Nervous System

Nervous System

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Board Coverage AQA Paper 2 | Edexcel A Paper 2 | OCR (A) Paper 2 | CIE Paper 4

1. Neuron Structure

1.1 Types of Neurone

The nervous system contains three functional types of neurone:

Type	Structure	Function
Sensory (afferent) neurone	Long axon; cell body in ganglion near CNS	Carries impulses from receptors to the CNS
Motor (efferent) neurone	Cell body in CNS; long axon to effector	Carries impulses from CNS to effectors (muscles, glands)
Relay (intermediate) neurone	Short axon; cell body entirely within CNS	Connects sensory and motor neurones within the CNS

Structural features common to all neurones:

• Cell body (soma): contains the nucleus, mitochondria, ribosomes, and other organelles. Site of protein synthesis.
• Dendrites: branched extensions that receive impulses from other neurones and transmit them towards the cell body.
• Axon: a single, long cytoplasmic extension that transmits impulses away from the cell body. Surrounded by a fatty insulating sheath (myelin).
• Axon terminals (synaptic knobs): branched endings that form synaptic junctions with the next neurone or effector.

1.2 Myelination

Many axons are surrounded by a myelin sheath, a lipid-rich insulating layer formed by Schwann cells (in the peripheral nervous system) or oligodendrocytes (in the central nervous system). The myelin sheath is not continuous; gaps between Schwann cells are called nodes of Ranvier (approximately $1$--$3\ \mu\mathrm{m}$ apart).

Myelination has two critical effects:

1. Electrical insulation: the myelin sheath prevents ion leakage across the membrane, maintaining the potential difference along the axon.
2. Saltatory conduction: action potentials jump from node to node (the only places where the axon membrane is exposed to the extracellular fluid), dramatically increasing the speed of transmission.

Feature	Myelinated Neurone	Non-Myelinated Neurone
Speed	$15$--$120\ \mathrm{m\ s^{-1}}$	$0.5$--$2\ \mathrm{m\ s^{-1}}$
Conduction	Saltatory (jumping between nodes)	Continuous wave of depolarisation
Energy consumption	Lower (fewer ions need to be pumped)	Higher (more $\mathrm{Na^+/K^+}$ pump activity)

warning

Common Pitfall Students often write that "myelin speeds up the action potential." More precisely, myelin forces the action potential to jump between nodes of Ranvier (saltatory conduction), which is much faster than continuous propagation. The speed increase is because less membrane needs to be depolarised, and the local current flows further ahead to depolarise the next node.

2. Resting Potential

2.1 Establishing the Resting Potential

The resting potential is the electrical potential difference across the membrane of a resting neurone, with the inside being approximately $-70\ \mathrm{mV}$ relative to the outside. This is maintained by the sodium-potassium pump and differential membrane permeability.

The sodium-potassium pump ($\mathrm{Na^+/K^+}$ ATPase) actively transports ions:

• Moves $3\ \mathrm{Na^+}$ out of the cell.
• Moves $2\ \mathrm{K^+}$ in.
• Uses one ATP per cycle.

This creates two concentration gradients:

Ion	Extracellular Concentration	Intracellular Concentration	Gradient
$\mathrm{Na^+}$	$\approx 145\ \mathrm{mmol\ dm^{-3}}$	$\approx 12\ \mathrm{mmol\ dm^{-3}}$	Outward (10:1)
$\mathrm{K^+}$	$\approx 4\ \mathrm{mmol\ dm^{-3}}$	$\approx 155\ \mathrm{mmol\ dm^{-3}}$	Inward (40:1)

The resting membrane is much more permeable to $\mathrm{K^+}$ than to $\mathrm{Na^+}$ (due to more $\mathrm{K^+}$ leak channels). $\mathrm{K^+}$ diffuses out of the cell down its concentration gradient, carrying positive charge with it. This makes the inside negative relative to the outside. The resting potential is close to the equilibrium potential for $\mathrm{K^+}$ (approximately $-90\ \mathrm{mV}$), but is slightly less negative (around $-70\ \mathrm{mV}$) because of a small inward leak of $\mathrm{Na^+}$.

2.2 Quantifying the Resting Potential: The Nernst Equation

The equilibrium potential for an ion is given by the Nernst equation:

$E = \frac{RT}{zF} \ln\frac◆LB◆[\text{ion}]_{\text{out}}◆RB◆◆LB◆[\text{ion}]_{\text{in}}◆RB◆$

where $R = 8.314\ \mathrm{J\ mol^{-1}\ K^{-1}}$, $T$ is temperature in Kelvin, $z$ is the ion's charge, and $F = 96485\ \mathrm{C\ mol^{-1}}$.

At body temperature ($37\ ^\circ\mathrm{C} = 310\ \mathrm{K}$):

$E_{\mathrm{K}} = \frac◆LB◆8.314 \times 310◆RB◆◆LB◆1 \times 96485◆RB◆ \ln\frac{4}{155} = 0.0267 \times \ln(0.0258) = 0.0267 \times (-3.66) = -97.7\ \mathrm{mV}$

$E_{\mathrm{Na}} = \frac◆LB◆8.314 \times 310◆RB◆◆LB◆1 \times 96485◆RB◆ \ln\frac{145}{12} = 0.0267 \times \ln(12.08) = 0.0267 \times 2.49 = +66.5\ \mathrm{mV}$

The actual resting potential ($-70\ \mathrm{mV}$) lies between $E_{\mathrm{K}}$ and $E_{\mathrm{Na}}$, weighted by the relative permeabilities.

3. Action Potentials

3.1 Depolarisation and the All-or-Nothing Principle

An action potential is a rapid reversal of the membrane potential from approximately $-70\ \mathrm{mV}$ to approximately $+40\ \mathrm{mV}$, followed by a return to the resting potential.

Stages of the action potential:

1. Depolarisation: a stimulus causes voltage-gated $\mathrm{Na^+}$ channels to open. $\mathrm{Na^+}$ ions rush into the axon down their electrochemical gradient (attracted by the negative interior and by the higher external concentration). The membrane potential rapidly depolarises from $-70\ \mathrm{mV}$ to $+40\ \mathrm{mV}$.

2. Repolarisation: at approximately $+40\ \mathrm{mV}$, the voltage-gated $\mathrm{Na^+}$ channels close and voltage-gated $\mathrm{K^+}$ channels open. $\mathrm{K^+}$ ions rush out of the axon down their concentration gradient, carrying positive charge out and restoring the negative interior.

3. Hyperpolarisation (overshoot): the $\mathrm{K^+}$ channels are slow to close, so $\mathrm{K^+}$ continues to diffuse out after the resting potential has been reached, making the inside temporarily more negative than $-70\ \mathrm{mV}$ (approximately $-80\ \mathrm{mV}$).

4. Restoring the resting potential: the $\mathrm{K^+}$ channels close, and the $\mathrm{Na^+/K^+}$ pump restores the original ion concentrations (this is slower and uses ATP).

The all-or-nothing principle: a stimulus must reach a threshold value (approximately $-55\ \mathrm{mV}$) to trigger an action potential. A sub-threshold stimulus produces no action potential. Once threshold is reached, the action potential is always the same size ($+40\ \mathrm{mV}$) -- it does not increase with stronger stimuli. The intensity of a stimulus is encoded in the frequency of action potentials, not their amplitude.

3.2 The Refractory Period

After an action potential, the neurone enters a refractory period during which it cannot be stimulated to fire another action potential:

• Absolute refractory period: voltage-gated $\mathrm{Na^+}$ channels are inactivated (they cannot reopen immediately). No stimulus, however strong, can generate a new action potential. This ensures action potentials travel in one direction only.
• Relative refractory period: the $\mathrm{Na^+}$ channels have recovered but the membrane is hyperpolarised (more negative than resting). An action potential can be generated only by a stronger-than-normal stimulus.

3.3 Propagation of the Action Potential

Action potentials are propagated along the axon by local currents. When one region of the membrane is depolarised, the positive charges inside flow laterally to adjacent regions, depolarising them to threshold and triggering a new action potential. The region behind the action potential is refractory, preventing backward propagation.

Factors affecting conduction velocity:

• Axon diameter: larger axons have lower internal resistance, allowing faster current flow. Conduction velocity is proportional to the square root of axon diameter.
• Myelination: saltatory conduction in myelinated axons is much faster ($15$--$120\ \mathrm{m\ s^{-1}}$) than continuous conduction in non-myelinated axons ($0.5$--$2\ \mathrm{m\ s^{-1}}$).

3.4 Worked Example: Calculating Conduction Velocity

An action potential is recorded at two points on an axon separated by $8.0\ \mathrm{cm}$. The time between the two recordings is $2.0\ \mathrm{ms}$.

$\text{Velocity} = \frac◆LB◆\text{distance}◆RB◆◆LB◆\text{time}◆RB◆ = \frac◆LB◆0.080\ \mathrm{m}◆RB◆◆LB◆0.002\ \mathrm{s}◆RB◆ = 40\ \mathrm{m\ s^{-1}}$

This is consistent with a myelinated axon of moderate diameter.

4. Synaptic Transmission

4.1 Structure of a Synapse

A synapse is the junction between two neurones (or between a neurone and an effector). The gap between the cells is the synaptic cleft (approximately $20$--$30\ \mathrm{nm}$ wide). The neurone before the synapse is the presynaptic neurone; the one after is the postsynaptic neurone.

Key structures:

• Synaptic vesicles: in the presynaptic terminal, containing neurotransmitter molecules.
• Presynaptic membrane: contains voltage-gated $\mathrm{Ca^{2+}}$ channels.
• Synaptic cleft: the gap filled with extracellular fluid.
• Postsynaptic membrane: contains receptor proteins (ligand-gated ion channels) specific to the neurotransmitter.
• Mitochondria: in the presynaptic terminal, providing ATP for neurotransmitter synthesis and vesicle recycling.

4.2 Mechanism of Synaptic Transmission

1. An action potential arrives at the presynaptic terminal.
2. The depolarisation opens voltage-gated $\mathrm{Ca^{2+}}$ channels in the presynaptic membrane.
3. $\mathrm{Ca^{2+}}$ ions diffuse into the presynaptic terminal down their concentration gradient.
4. The influx of $\mathrm{Ca^{2+}}$ causes synaptic vesicles to fuse with the presynaptic membrane (exocytosis), releasing neurotransmitter into the synaptic cleft.
5. The neurotransmitter diffuses across the synaptic cleft and binds to specific receptor proteins on the postsynaptic membrane.
6. Binding opens ligand-gated ion channels on the postsynaptic membrane:
   • If $\mathrm{Na^+}$ channels open: $\mathrm{Na^+}$ enters the postsynaptic neurone, causing depolarisation (excitatory postsynaptic potential, EPSP).
   • If $\mathrm{Cl^-}$ channels open: $\mathrm{Cl^-}$ enters (or $\mathrm{K^+}$ exits), causing hyperpolarisation (inhibitory postsynaptic potential, IPSP).
7. If the combined EPSPs reach threshold ($-55\ \mathrm{mV}$), an action potential is triggered in the postsynaptic neurone.
8. The neurotransmitter is rapidly removed from the synaptic cleft by: enzymatic breakdown (e.g., acetylcholinesterase breaks down acetylcholine); reuptake into the presynaptic neurone; diffusion away from the synapse.

4.3 Excitatory and Inhibitory Synapses

Feature	Excitatory Synapse	Inhibitory Synapse
Neurotransmitter example	Acetylcholine (at neuromuscular junction), glutamate	GABA (in the brain), glycine
Ion channels opened	$\mathrm{Na^+}$ channels (sometimes also $\mathrm{Ca^{2+}}$)	$\mathrm{Cl^-}$ channels (sometimes $\mathrm{K^+}$ channels)
Effect on postsynaptic membrane	Depolarisation (EPSP) -- moves closer to threshold	Hyperpolarisation (IPSP) -- moves further from threshold
Net effect	Increases likelihood of action potential	Decreases likelihood of action potential

4.4 Summation

A single EPSP is usually insufficient to reach threshold. The postsynaptic neurone integrates (sums) multiple inputs:

• Spatial summation: multiple presynaptic neurones release neurotransmitter simultaneously onto the same postsynaptic neurone. The combined depolarisation from several EPSPs reaches threshold.
• Temporal summation: a single presynaptic neurone fires action potentials in rapid succession. The EPSPs overlap and add together before the first one decays, reaching threshold.

warning

Common Pitfall Students often write that "neurotransmitters cross the synaptic cleft by diffusion" without specifying that they bind to receptors. The neurotransmitter diffuses across the cleft and binds to specific receptor proteins on the postsynaptic membrane. This binding opens ion channels, which is what causes the change in membrane potential. The specificity of neurotransmitter-receptor binding is what determines whether the synapse is excitatory or inhibitory.

5. Neurotransmitters

5.1 Acetylcholine

Acetylcholine (ACh) is the neurotransmitter at:

• Neuromuscular junctions (between motor neurones and muscle fibres) -- always excitatory.
• Many synapses within the CNS -- can be excitatory or inhibitory depending on the receptor.
• Synapses in the parasympathetic nervous system (e.g., stimulating digestion, slowing heart rate).

ACh is synthesised from choline and acetyl-CoA by the enzyme choline acetyltransferase. It is rapidly broken down in the synaptic cleft by acetylcholinesterase into choline and acetate, which are recycled by the presynaptic neurone. This rapid breakdown ensures that the signal is brief and precise.

5.2 Other Important Neurotransmitters

Neurotransmitter	Location	Function
Noradrenaline	Sympathetic nervous system	Fight-or-flight response; increases heart rate
Dopamine	Basal ganglia, reward pathways	Motor control, motivation, reward, pleasure
Serotonin	Brainstem, GI tract	Mood regulation, sleep, appetite, temperature
GABA	Brain (most common inhibitory)	Reduces neuronal excitability; prevents overactivity
Glutamate	Brain (most common excitatory)	Major excitatory neurotransmitter; involved in learning
Endorphins	Brain, pituitary	Natural pain relief; euphoria

5.3 Drugs and the Nervous System

Many drugs act by modifying synaptic transmission:

• Agonists: mimic the action of a neurotransmitter by binding to its receptors (e.g., nicotine mimics ACh at nicotinic receptors).
• Antagonists: block the action of a neurotransmitter by binding to receptors without activating them (e.g., curare blocks ACh receptors at the neuromuscular junction, causing paralysis).
• Enzyme inhibitors: prevent the breakdown of neurotransmitter, prolonging its effect (e.g., organophosphates inhibit acetylcholinesterase, causing continuous muscle contraction and paralysis; used as nerve agents and insecticides).
• Reuptake inhibitors: block the reuptake of neurotransmitter into the presynaptic neurone, increasing its concentration in the synaptic cleft (e.g., fluoxetine/Prozac blocks serotonin reuptake, used to treat depression).
• Stimulants: increase neurotransmitter release or receptor sensitivity (e.g., amphetamines increase dopamine and noradrenaline release).

6. Reflex Arcs

6.1 Structure of a Reflex Arc

A reflex arc is the pathway by which a reflex action (a rapid, involuntary response to a stimulus) is carried out. It does not involve conscious processing in the brain, allowing very fast responses that can be protective.

Components of a reflex arc:

1. Stimulus: a change in the environment detected by a receptor.
2. Receptor: a sensory cell that converts the stimulus into an electrical impulse (transduction).
3. Sensory neurone: transmits the impulse from the receptor to the CNS (spinal cord).
4. Relay neurone: (in some reflex arcs) connects the sensory neurone to the motor neurone within the CNS.
5. Motor neurone: transmits the impulse from the CNS to the effector.
6. Effector: a muscle or gland that carries out the response.
7. Response: the action taken by the effector (e.g., muscle contraction, gland secretion).

6.2 The Knee-Jerk Reflex (Stretch Reflex)

A monosynaptic reflex (only one synapse, between the sensory and motor neurone):

1. Tapping the patellar tendon stretches the quadriceps muscle.
2. Stretch receptors (muscle spindles) in the quadriceps detect the stretch and generate impulses.
3. Sensory neurones carry impulses to the spinal cord.
4. The sensory neurone synapses directly with a motor neurone (no relay neurone).
5. The motor neurone carries impulses to the quadriceps muscle, which contracts (causing the leg to kick).
6. Simultaneously, an inhibitory interneurone inhibits the motor neurone supplying the antagonistic hamstring muscle (reciprocal inhibition).

This reflex is used clinically to test the function of spinal segments L2--L4.

6.3 The Withdrawal Reflex

A polysynaptic reflex (involves at least one relay neurone):

1. A painful stimulus (e.g., touching a hot object) is detected by pain receptors (nociceptors) in the skin.
2. Sensory neurones transmit impulses to the spinal cord.
3. Relay neurones in the spinal cord activate motor neurones that supply the flexor muscles in the affected limb (causing withdrawal).
4. Simultaneously, inhibitory interneurones inhibit the motor neurones supplying the extensor muscles (reciprocal inhibition).
5. The limb is rapidly withdrawn from the painful stimulus before the brain has time to process the information consciously.

The brain is informed of the reflex action (by sensory neurones ascending to the brain), allowing conscious awareness and modification of the response, but the reflex itself is spinal.

warning

Common Pitfall Students often state that reflexes "do not involve the brain." Reflexes do not require brain processing to occur, but the brain receives sensory information about the reflex via ascending tracts. This allows the brain to modify the response if necessary (e.g., suppressing the withdrawal reflex if you are carrying something hot).

7. Sensory Receptors

7.1 Pacinian Corpuscles

Pacinian corpuscles are mechanoreceptors that detect pressure and vibration in the skin. They are found deep in the dermis and subcutaneous tissue.

Structure: each consists of the ending of a sensory neurone surrounded by concentric layers of connective tissue (lamellae) that form an onion-like capsule.

Mechanism of action:

1. When pressure is applied, the lamellae are deformed, stretching the neurone membrane.
2. The deformation opens stretch-mediated sodium channels in the membrane.
3. $\mathrm{Na^+}$ ions diffuse into the neurone, causing depolarisation.
4. This creates a generator potential (a local depolarisation, not an action potential).
5. If the generator potential reaches threshold, it triggers an action potential in the sensory neurone.
6. The action potential propagates along the sensory neurone to the CNS.

The generator potential is graded: stronger pressure produces larger depolarisation (more sodium channels open), increasing the frequency of action potentials. This allows the brain to perceive the intensity of the stimulus.

7.2 Other Receptor Types

Receptor Type	Stimulus Detected	Location
Mechanoreceptors	Pressure, vibration, sound	Skin, inner ear (cochlea)
Thermoreceptors	Temperature changes	Skin, hypothalamus
Chemoreceptors	Chemical concentration (e.g., $\mathrm{O_2}$, $\mathrm{CO_2}$, glucose, pH)	Carotid bodies, aortic bodies, taste buds, olfactory epithelium
Photoreceptors	Light	Retina (rods and cones)
Nociceptors	Pain (tissue damage)	Skin, joints, internal organs
Proprioceptors	Body position, limb movement	Muscles, tendons, joints

8. Muscle Contraction: The Sliding Filament Mechanism

8.1 Structure of Skeletal Muscle

Skeletal muscle is composed of muscle fibres (multinucleated cells formed by the fusion of many myoblasts). Each muscle fibre contains:

• Myofibrils: parallel, cylindrical organelles running the length of the fibre, composed of repeating units called sarcomeres.
• Sarcomere: the functional unit of muscle contraction, bounded by Z-lines. Contains two types of protein filament:
  • Thick filaments (myosin): composed of myosin molecules with globular heads that can bind to actin and hydrolyse ATP.
  • Thin filaments (actin): composed of actin monomers twisted into a double helix, with binding sites for myosin heads. Thin filaments also contain tropomyosin (which blocks myosin-binding sites on actin at rest) and troponin (which binds calcium and moves tropomyosin aside).

Banding pattern: the alternating arrangement of thick and thin filaments produces characteristic bands visible under light microscopy:

• A-band: the full length of the thick filament (dark).
• I-band: the region containing only thin filaments (light).
• H-zone: the central region of the A-band containing only thick filaments (no overlap).
• Z-line: the boundary between adjacent sarcomeres.

8.2 The Sliding Filament Theory

Muscle contraction occurs by the sliding of thin filaments past thick filaments, drawing the Z-lines closer together and shortening the sarcomere. The filaments themselves do not change length.

The cross-bridge cycle:

1. Calcium release: an action potential arrives at the neuromuscular junction (see Section 8.3) and triggers muscle contraction. The action potential travels along the sarcolemma (muscle cell membrane) and into T-tubules (invaginations of the sarcolemma), causing the sarcoplasmic reticulum to release $\mathrm{Ca^{2+}}$ ions into the sarcoplasm.

2. Calcium binds to troponin: $\mathrm{Ca^{2+}}$ binds to troponin, causing a conformational change that moves tropomyosin away from the myosin-binding sites on actin. The binding sites are now exposed.

3. Cross-bridge formation: the myosin head (which has already hydrolysed ATP to ADP + $P_i$ and is in a high-energy "cocked" position) binds to the exposed binding site on actin, forming a cross-bridge.

4. The power stroke: the myosin head pivots, pulling the thin filament towards the centre of the sarcomere. ADP and $P_i$ are released during this step.

5. ATP binding and cross-bridge detachment: a new ATP molecule binds to the myosin head, causing it to detach from actin.

6. ATP hydrolysis and re-cocking: ATP is hydrolysed to ADP + $P_i$, and the energy released re-cocks the myosin head to its high-energy position, ready for another cycle.

This cycle continues as long as $\mathrm{Ca^{2+}}$ and ATP are available. One power stroke moves the thin filament approximately $5$--$10\ \mathrm{nm}$.

8.3 The Neuromuscular Junction

The neuromuscular junction (NMJ) is a specialised cholinergic synapse between a motor neurone and a skeletal muscle fibre.

1. An action potential arrives at the motor neurone terminal.
2. Voltage-gated $\mathrm{Ca^{2+}}$ channels open; $\mathrm{Ca^{2+}}$ enters and triggers exocytosis of acetylcholine-containing vesicles.
3. ACh diffuses across the synaptic cleft and binds to nicotinic acetylcholine receptors on the muscle fibre membrane (motor end plate).
4. These receptors are ligand-gated $\mathrm{Na^+}$ channels. When ACh binds, they open, allowing $\mathrm{Na^+}$ to enter the muscle fibre.
5. The resulting depolarisation (end-plate potential) opens voltage-gated $\mathrm{Na^+}$ channels in the adjacent membrane, triggering an action potential that propagates along the sarcolemma and into T-tubules.
6. Acetylcholinesterase in the synaptic cleft rapidly breaks down ACh, terminating the signal.

8.4 Energy and Muscle Contraction

Muscle contraction requires ATP for:

• The cross-bridge cycle (myosin head detachment and re-cocking).
• The $\mathrm{Ca^{2+}}$ pump (SERCA) that actively transports $\mathrm{Ca^{2+}}$ back into the sarcoplasmic reticulum, ending contraction.
• The $\mathrm{Na^+/K^+}$ pump that restores ion gradients after action potentials.

ATP is regenerated by:

• Aerobic respiration: in mitochondria (for sustained, moderate activity).
• Anaerobic glycolysis: produces ATP rapidly but also generates lactate (for intense, short-duration activity). See Respiration.
• Creatine phosphate: a rapidly mobilised phosphate store in muscle. Creatine phosphate transfers its phosphate group to ADP, regenerating ATP almost instantly: $\mathrm{Creatine\ phosphate + ADP \rightleftharpoons creatine + ATP}$ This provides ATP for approximately the first 5--10 seconds of intense activity.

9. Nervous Control of Heart Rate

9.1 The Autonomic Nervous System

Heart rate is controlled involuntarily by the autonomic nervous system (ANS), which has two antagonistic divisions:

Feature	Sympathetic Nervous System	Parasympathetic Nervous System
General role	Fight-or-flight; increases activity	Rest-and-digest; decreases activity
Neurotransmitter at target	Noradrenaline	Acetylcholine
Effect on heart rate	Increases (accelerates)	Decreases (decelerates)
Effect on cardiac output	Increases (via increased rate and stroke volume)	Decreases (via decreased rate)

9.2 Control Centre: The Medulla Oblongata

The cardiovascular centre in the medulla oblongata (in the brainstem) coordinates heart rate:

• The acceleratory centre sends impulses via the sympathetic nervous system to the sinoatrial node (SAN), increasing heart rate.
• The inhibitory centre sends impulses via the vagus nerve (parasympathetic) to the SAN, decreasing heart rate.

9.3 Factors Influencing Heart Rate

Chemoreceptors in the aortic body and carotid body detect changes in blood chemistry:

• Low $p\mathrm{O_2}$, high $p\mathrm{CO_2}$, or low pH (high $\mathrm{H^+}$ concentration): detected by chemoreceptors, which send impulses to the cardiovascular centre. The centre increases sympathetic stimulation and decreases parasympathetic stimulation, increasing heart rate to increase blood flow to the lungs for gas exchange.

Baroreceptors (pressure receptors) in the aortic arch and carotid sinus detect changes in blood pressure:

• High blood pressure: baroreceptors are stretched more, sending more impulses to the cardiovascular centre. The centre increases parasympathetic stimulation and decreases sympathetic stimulation, slowing the heart rate to reduce blood pressure.
• Low blood pressure: reduced baroreceptor stimulation leads to increased sympathetic output and decreased parasympathetic output, increasing heart rate to restore blood pressure.

For more detail on the cardiac cycle and pressure changes, see Exchange and Transport.

10. Brain Structure and Function

10.1 Major Brain Regions

Region	Location	Key Functions
Cerebrum	Largest part; two hemispheres	Conscious thought, memory, language, decision-making, sensory processing, voluntary movement
Cerebellum	Below the cerebrum; at the back	Coordination of movement, balance, posture, fine motor control
Medulla oblongata	Base of the brainstem	Control of breathing rate, heart rate, blood pressure (autonomic functions)
Hypothalamus	Below the thalamus	Thermoregulation, osmoregulation (ADH release), hunger, thirst, circadian rhythm
Thalamus	Above the hypothalamus	Relay station for sensory information to the cerebrum; filters sensory input
Pituitary gland	Below the hypothalamus	Hormone secretion (ACTH, TSH, FSH, LH, growth hormone, ADH); "master gland"

10.2 The Cerebral Cortex

The cerebral cortex is the outer layer of the cerebrum, approximately $2$--$4\ \mathrm{mm}$ thick, containing cell bodies of neurones (grey matter). It is divided into functional areas:

• Motor cortex (frontal lobe): controls voluntary movement of skeletal muscles. The area is mapped to specific body parts (the motor homunculus).
• Somatosensory cortex (parietal lobe): receives and processes sensory information from the skin (touch, pressure, temperature, pain).
• Visual cortex (occipital lobe): processes visual information from the eyes.
• Auditory cortex (temporal lobe): processes auditory information from the ears.
• Prefrontal cortex (anterior frontal lobe): higher cognitive functions: planning, decision-making, personality, social behaviour.

11. Neurodegenerative Diseases

11.1 Alzheimer's Disease

Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia.

Pathology:

• Amyloid plaques: deposits of beta-amyloid peptide ($\mathrm{A\beta_{42}}$) accumulate in the spaces between neurones. These plaques are toxic to neurones and disrupt synaptic function.
• Neurofibrillary tangles: hyperphosphorylated tau protein accumulates inside neurones, disrupting the microtubule transport system that normally moves organelles and molecules along the axon.
• Loss of cholinergic neurones: neurones using acetylcholine in the cerebral cortex and hippocampus degenerate, reducing ACh levels and impairing memory and cognition.

Symptoms: progressive memory loss (especially short-term), confusion, language difficulties, personality changes, loss of ability to perform daily tasks. The hippocampus (essential for forming new memories) is affected early.

Risk factors: age (greatest risk factor), genetics (APOE4 allele), cardiovascular disease, head injury.

11.2 Parkinson's Disease

Parkinson's disease results from the progressive death of dopamine-producing neurones in the substantia nigra (part of the basal ganglia, involved in movement control).

Pathology: loss of dopaminergic neurones reduces dopamine levels in the basal ganglia, disrupting the balance between excitation and inhibition of motor pathways.

Symptoms: tremor (especially at rest), bradykinesia (slowness of movement), rigidity (stiff muscles), postural instability, reduced facial expression. Non-motor symptoms include depression, sleep disturbances, and cognitive decline.

Treatment: L-DOPA (a precursor of dopamine that can cross the blood-brain barrier); dopamine agonists; deep brain stimulation.

11.3 Motor Neurone Disease (MND)

MND (amyotrophic lateral sclerosis, ALS) involves the progressive degeneration of both upper motor neurones (in the motor cortex) and lower motor neurones (in the brainstem and spinal cord). This leads to progressive muscle weakness, wasting, and eventual paralysis, including respiratory failure. The cause is not fully understood but involves a combination of genetic and environmental factors.

Practice Problems

Details

Problem 1

Describe the events that occur at a cholinergic synapse when an action potential arrives at the presynaptic terminal. (6 marks)

Answer. (1) The action potential depolarises the presynaptic membrane, opening voltage-gated $\mathrm{Ca^{2+}}$ channels. (2) $\mathrm{Ca^{2+}}$ ions diffuse into the presynaptic terminal down their electrochemical gradient. (3) The influx of $\mathrm{Ca^{2+}}$ causes synaptic vesicles containing acetylcholine to move to and fuse with the presynaptic membrane (exocytosis), releasing ACh into the synaptic cleft. (4) ACh diffuses across the synaptic cleft and binds to specific receptor proteins (nicotinic receptors, which are ligand-gated $\mathrm{Na^+}$ channels) on the postsynaptic membrane. (5) The binding opens the $\mathrm{Na^+}$ channels; $\mathrm{Na^+}$ ions flow into the postsynaptic neurone, causing depolarisation (an excitatory postsynaptic potential). (6) If threshold is reached, an action potential is triggered in the postsynaptic neurone. (7) Acetylcholinesterase in the synaptic cleft hydrolyses ACh into choline and acetate, which are reabsorbed by the presynaptic neurone, terminating the signal.

If you get this wrong, revise: Mechanism of Synaptic Transmission

Details

Problem 2

Explain the sliding filament theory of muscle contraction. In your answer, describe the roles of calcium ions, ATP, tropomyosin, and troponin. (6 marks)

Answer. When an action potential reaches a muscle fibre, it travels along the sarcolemma into T-tubules, triggering the sarcoplasmic reticulum to release $\mathrm{Ca^{2+}}$ into the sarcoplasm. Calcium ions bind to troponin, causing a conformational change that moves tropomyosin away from the myosin-binding sites on actin filaments, exposing them. The myosin heads (which have already hydrolysed ATP to ADP + $P_i$ and are in a high-energy cocked position) bind to the exposed sites on actin, forming cross-bridges. The myosin heads pivot (the power stroke), pulling the thin filaments towards the centre of the sarcomere and releasing ADP + $P_i$. A new molecule of ATP binds to the myosin head, causing it to detach from actin. The ATP is hydrolysed, re-cocking the myosin head for another cycle. This process continues as long as $\mathrm{Ca^{2+}}$ and ATP are available. The sliding of filaments shortens each sarcomere, and the combined shortening of all sarcomeres shortens the entire muscle fibre, producing contraction.

If you get this wrong, revise: The Sliding Filament Theory

Details

Problem 3

Explain how the refractory period ensures that action potentials travel in one direction only along an axon, and why this is important. (4 marks)

Answer. During the absolute refractory period, the voltage-gated sodium channels behind the action potential are inactivated and cannot reopen. This means the region of the axon that has just been depolarised cannot be depolarised again immediately. When local currents from the action potential spread ahead (in the forward direction), they depolarise the next region of membrane to threshold, triggering a new action potential. When the currents spread backwards, they encounter membrane in the refractory state and cannot depolarise it to threshold. This ensures unidirectional propagation of the action potential from the cell body towards the axon terminals. Unidirectional transmission is essential for the orderly flow of information in the nervous system, ensuring that signals reach the correct target.

If you get this wrong, revise: The Refractory Period

Details

Problem 4

A person's blood pressure rises sharply. Describe the sequence of events by which the nervous system detects this change and restores normal blood pressure. (5 marks)

Answer. The rise in blood pressure is detected by baroreceptors (pressure receptors) in the aortic arch and carotid sinus. The increased blood pressure causes greater stretching of the baroreceptor walls, which increases the frequency of action potentials sent to the cardiovascular centre in the medulla oblongata. The cardiovascular centre responds by increasing parasympathetic (vagus nerve) stimulation to the sinoatrial node (SAN) and decreasing sympathetic stimulation. Acetylcholine released by parasympathetic neurones at the SAN slows the rate of depolarisation of the SAN, reducing heart rate. The decreased heart rate reduces cardiac output, which lowers blood pressure back towards normal. This is an example of negative feedback.

If you get this wrong, revise: Nervous Control of Heart Rate

Details

Problem 5

Explain how spatial and temporal summation enable a postsynaptic neurone to reach threshold and fire an action potential. (4 marks)

Answer. A single excitatory postsynaptic potential (EPSP) typically produces a depolarisation of a few millivolts, which is insufficient to reach the threshold of approximately $-55\ \mathrm{mV}$. Spatial summation occurs when multiple presynaptic neurones release neurotransmitter simultaneously onto different parts of the same postsynaptic neurone. The EPSPs generated at different synapses on the postsynaptic neurone add together (summate), producing a larger depolarisation that may reach threshold. Temporal summation occurs when a single presynaptic neurone fires rapidly, releasing neurotransmitter in quick succession. Each EPSP begins before the previous one has fully decayed, so the depolarisations build on each other, producing a larger cumulative depolarisation. Both mechanisms allow the nervous system to integrate multiple inputs and fire action potentials only when sufficient excitatory input is received.

If you get this wrong, revise: Summation

12. Detailed Neurone Physiology

12.1 The Refractory Period in Detail

The refractory period has critical functional consequences:

1. Unidirectional propagation: during the absolute refractory period, the sodium channels behind the action potential are inactivated. Local currents from the active region cannot depolarise this region to threshold because the channels cannot reopen. This forces the action potential to propagate in one direction only -- from the cell body towards the axon terminals.

2. Frequency coding: the refractory period limits the maximum frequency at which action potentials can fire. If the absolute refractory period is approximately $1\ \mathrm{ms}$, the maximum firing rate is approximately $1000$ action potentials per second. In practice, the relative refractory period extends the minimum interval between action potentials, reducing the maximum rate further.

3. Prevention of tetanus: skeletal muscles stimulated by nerve impulses at high frequency undergo sustained contraction (tetanus) because calcium remains in the sarcoplasm. However, individual action potentials remain discrete because each must wait for the refractory period before the next can be generated. This is why nerve impulses are always all-or-nothing events, not graded responses.

12.2 Myelination and Conduction Velocity

The relationship between axon diameter and conduction velocity for myelinated and non-myelinated axons is approximately:

• Non-myelinated: $v \approx k \cdot d^{0.5}$ (velocity proportional to the square root of diameter)
• Myeliated: $v \approx 6 \cdot d$ (velocity approximately proportional to diameter)

The much steeper relationship for myelinated axons means that larger myelinated axons have disproportionately faster conduction velocities. This is why the largest axons in the nervous system (e.g., the giant squid axon, diameter $\approx 500\ \mu\mathrm{m}$) are unmyelinated -- at such large diameters, the increased resistance per unit length is less significant.

12.3 Local Currents and Cable Theory

The depolarisation at one point on the axon membrane creates a circuit with the adjacent, still-polarised region. Current flows from the depolarised region (positive inside) to the adjacent polarised region (negative inside), completing the circuit through the extracellular fluid.

The distance an action potential can propagate without being too attenuated depends on the length constant ($\lambda$):

$\lambda = \sqrt◆LB◆\frac{r_m}{r_i + r_o}◆RB◆$

where $r_m$ is the membrane resistance ($\Omega \cdot \mathrm{cm}$), $r_i$ is the intracellular (axial) resistance ($\Omega\ \mathrm{cm^{-1}}$), and $r_o$ is the extracellular resistance.

For myelinated axons, $r_m$ is very high (due to the insulating myelin sheath), so $\lambda$ is very large. This means the depolarisation can spread further without attenuation, and saltatory conduction is efficient.

13. Synaptic Integration

13.1 EPSPs and IPSPs

Excitatory postsynaptic potentials (EPSPs) are local, graded depolarisations of the postsynaptic membrane caused by the opening of ligand-gated $\mathrm{Na^+}$ channels. Typical amplitude: $0.5$--$5\ \mathrm{mV}$. Duration: $5$--$20\ \mathrm{ms}$.

Inhibitory postsynaptic potentials (IPSPs) are local, graded hyperpolarisations caused by the opening of $\mathrm{Cl^-}$ channels (or $\mathrm{K^+}$ channels). Typical amplitude: $1$--$5\ \mathrm{mV}$ hyperpolarisation. Duration: $10$--$30\ \mathrm{ms}$.

13.2 The Postsynaptic Membrane as an Integrator

The postsynaptic neurone's membrane acts as an integrator, summing all incoming EPSPs and IPSPs at the axon hillock (the region where the axon meets the cell body). The axon hillock has the highest density of voltage-gated $\mathrm{Na^+}$ channels and therefore the lowest threshold for action potential initiation.

An action potential is fired only when the net depolarisation at the axon hillock reaches threshold ($\approx -55\ \mathrm{mV}$). This requires the sum of EPSPs minus the sum of IPSPs to exceed threshold.

13.3 Facilitation and Long-Term Potentiation

Synaptic facilitation: repeated stimulation of a synapse at high frequency increases the amount of neurotransmitter released per action potential (due to residual $\mathrm{Ca^{2+}}$ in the presynaptic terminal). This enhances the postsynaptic response -- each successive EPSP is slightly larger than the previous one. This is a form of short-term memory at the synaptic level.

Long-term potentiation (LTP): persistent strengthening of a synapse following high-frequency stimulation. LTP involves:

1. High-frequency stimulation of a presynaptic neurone causes large, sustained increases in $\mathrm{Ca^{2+}}$ in the postsynaptic neurone.
2. The $\mathrm{Ca^{2+}}$ activates CaMKII (calcium/calmodulin-dependent protein kinase II), which phosphorylates AMPA receptors, increasing their conductance.
3. More AMPA receptors are inserted into the postsynaptic membrane.
4. NMDA receptors (a type of glutamate receptor that is both ligand-gated and voltage-gated) play a key role: they are only activated when the postsynaptic membrane is already depolarised (by AMPA receptor-mediated EPSPs) and glutamate is bound. This makes NMDA receptors coincidence detectors -- they are activated only when the presynaptic neurone fires repeatedly at high frequency.

LTP is considered a cellular mechanism for learning and memory in the hippocampus.

14. The Eye and Photoreceptors

14.1 Retinal Structure

The retina contains two types of photoreceptor:

Rods:

• Responsible for vision in low light (scotopic vision).
• Approximately 120 million per eye, concentrated in the periphery.
• Contain the pigment rhodopsin (composed of retinal and opsin).
• Sensitive to a broad range of wavelengths (peak at approximately $500\ \mathrm{nm}$, blue-green light).
• Low spatial resolution (many rods converge onto a single bipolar cell via convergence).
• Cannot distinguish colour (only one type of photopigment).

Cones:

• Responsible for colour vision and high-acuity vision (photopic vision).
• Approximately 6 million per eye, concentrated in the fovea (centre of the retina).
• Three types, each containing a different photopigment sensitive to different wavelengths:
  • S-cones (blue): peak sensitivity at $\approx 430\ \mathrm{nm}$.
  • M-cones (green): peak sensitivity at $\approx 530\ \mathrm{nm}$.
  • L-cones (red): peak sensitivity at $\approx 560\ \mathrm{nm}$.
• High spatial resolution (fewer cones per bipolar cell in the fovea; 1:1 ratio).
• Require brighter light to function (explain why colour vision is poor in dim light).

14.2 Phototransduction

When light strikes a photoreceptor:

1. A photon is absorbed by the photopigment (rhodopsin in rods).
2. The pigment bleaches (retinal isomerises from 11-cis to all-trans configuration).
3. This activates transducin (a G-protein), which activates phosphodiesterase (PDE).
4. PDE breaks down cGMP to GMP.
5. The decrease in cGMP causes Na$^+$ channels to close.
6. The cell hyperpolarises (becomes more negative inside).
7. Reduced neurotransmitter release signals to bipolar cells that light has been detected.

14.3 The Fovea and Visual Acuity

The fovea is a small depression at the centre of the retina where cones are most densely packed. Each cone connects to a single bipolar cell and a single ganglion cell (1:1:1 pathway), providing maximum spatial resolution. However, the fovea contains no rods, which is why peripheral vision is poor in dim light but central vision has high acuity.

15. Hormonal and Nervous System Interactions

15.1 Adrenal Glands

The adrenal glands sit on top of the kidneys and have two functionally distinct regions:

Adrenal cortex (outer region, controlled by ACTH from the pituitary):

• Produces mineralocorticoids (e.g., aldosterone), which regulates $\mathrm{Na^+}$ reabsorption in the kidneys.
• Produces glucocorticoids (e.g., cortisol), which regulates metabolism, suppresses the immune system, and responds to stress.

Adrenal medulla (inner region, controlled by the sympathetic nervous system):

• Produces adrenaline (epinephrine) and noradrenaline (norepinephrine) -- catecholamine hormones that mediate the fight-or-flight response.
• Secretion is controlled directly by sympathetic preganglionic neurones (not by hormones), making the adrenal medulla a specialised neuroendocrine organ.

15.2 The Fight-or-Flight Response

Perceived threat $\to$ hypothalamus $\to$ sympathetic nervous system $\to$ adrenal medulla + target organs:

Effect	Mechanism
Increased heart rate	Sympathetic stimulation of SAN; adrenaline on $\beta_1$ receptors
Increased ventilation	Sympathetic stimulation of respiratory muscles
Pupil dilation	Radial muscle contraction (sympathetic)
Bronchodilation	Relaxation of bronchial smooth muscle
Vasoconstriction of skin	Redirects blood to muscles and brain
Vasodilation of skeletal muscle	Increased blood flow to muscles
Glycogenolysis in liver	Adrenaline stimulates breakdown of glycogen to glucose
Increased blood glucose	Adrenaline inhibits insulin secretion; stimulates glucagon secretion
Inhibition of digestion	Reduced blood flow to gut; decreased gut motility
Increased mental alertness	Adrenaline acts on the brain; pupils dilate for wider visual field

For more on hormonal control of blood glucose, see Homeostasis.

16. Invertebrate Nervous Systems

16.1 Comparison with Vertebrate Nervous Systems

Feature	Vertebrate Nervous System	Invertebrate Nervous System (e.g., insect)
Organisation	Central (brain + spinal cord) + peripheral	Ventral nerve cord + ganglia
Neurone structure	Myelinated; saltatory conduction	Non-myelinated; slower conduction
Speed	Fast ($15$--$120\ \mathrm{m\ s^{-1}}$)	Slower ($0.5$--$10\ \mathrm{m\ s^{-1}}$)
Giant axons	Rare (some in vertebrates)	Common (squid giant axon, $500\ \mu\mathrm{m}$)
Cell bodies	In CNS	In ganglia (peripheral)

16.2 The Squid Giant Axon

The giant axon of the squid (Loligo forbesii) was instrumental in the discovery of the ionic basis of the action potential (Hodgkin and Huxley, 1952; Nobel Prize 1963). Its large diameter ($\approx 500\ \mu\mathrm{m}$) allowed insertion of microelectrodes for intracellular recording, which was not possible with smaller vertebrate axons at the time.

Hodgkin and Huxley used the voltage clamp technique to hold the membrane potential at a fixed value and measure the ionic currents flowing across the membrane. This allowed them to determine the conductances of the $\mathrm{Na^+}$ and $\mathrm{K^+}$ channels as a function of membrane potential, establishing the Hodgkin-Huxley equations that describe the action potential quantitatively.

17. Drugs Affecting Synaptic Transmission

17.1 Detailed Mechanisms

Nicotine (from tobacco) binds to nicotinic ACh receptors (ligand-gated $\mathrm{Na^+}$ channels) in the brain, causing $\mathrm{Na^+}$ influx and depolarisation. Prolonged exposure causes receptor up-regulation (increased number of receptors), which contributes to tolerance and addiction.

Cocaine blocks the reuptake of dopamine from the synaptic cleft by the dopamine transporter (DAT). Dopamine accumulates in the synapse, overstimulating postsynaptic receptors. Chronic use causes down-regulation of dopamine receptors and depletion of dopamine reserves, contributing to the "crash" and addiction cycle.

Serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine/Prozac) block the serotonin transporter (SERT), increasing serotonin concentration in the synaptic cleft. This enhances serotonergic neurotransmission, which is thought to alleviate depression by increasing neurotransmission in brain circuits that regulate mood, emotion, and sleep.

Benzodiazepines (e.g., diazepam/Valium) enhance the effect of GABA (the main inhibitory neurotransmitter in the brain). They bind to a specific site on the $\mathrm{GABA_A}$ receptor, increasing the frequency of chloride channel opening, increasing hyperpolarisation of the postsynaptic membrane. This produces anxiolytic (anti-anxiety), sedative, and muscle-relaxant effects.

17.2 Tolerance and Dependence

Tolerance: repeated exposure to a drug reduces its effect. Mechanisms include receptor down-regulation (fewer receptors), metabolic tolerance (faster drug breakdown), and behavioural tolerance (learned compensatory responses).

Dependence: the body adapts to the continued presence of a drug, so that removal causes withdrawal symptoms. Physical dependence involves neuroadaptation; psychological dependence involves craving and compulsive drug-seeking behaviour.

18. The Brain: Structure and Function

18.1 Major Brain Regions

Region	Location	Key Functions
Cerebrum	Largest part, divided into left and right cerebral hemispheres	Conscious thought, memory, language, decision-making, sensory processing, voluntary movement
Cerebellum	Below the cerebrum, behind the brainstem	Coordination of movement, balance, posture, motor learning
Medulla oblongata	Lowest part of the brainstem	Controls autonomic functions: heart rate, breathing rate (ventilation centre), blood pressure (vasomotor centre), swallowing, coughing, sneezing
Hypothalamus	Below the thalamus, above the pituitary	Thermoregulation, osmoregulation, control of pituitary hormone release, hunger and thirst, sleep-wake cycles
Thalamus	Central relay station above the hypothalamus	Relays sensory information (except olfaction) to the appropriate area of the cerebrum; involved in consciousness and alertness
Corpus callosum	Band of nerve fibres connecting the two cerebral hemispheres	Communication between left and right hemispheres

18.2 The Cerebral Cortex

The outer layer of the cerebrum is the cerebral cortex (approximately 2--4 mm thick), which is highly folded (gyri = ridges, sulci = grooves) to increase surface area. It is divided into four lobes:

Lobe	Location	Primary Functions
Frontal	Front of the brain, behind the forehead	Motor cortex (voluntary movement), prefrontal cortex (decision-making, planning, personality), Broca's area (speech production -- left hemisphere in most people)
Parietal	Behind the frontal lobe	Somatosensory cortex (touch, pressure, temperature, pain perception from the body)
Temporal	Side of the brain, below the parietal lobe	Primary auditory cortex (hearing), Wernicke's area (speech comprehension -- left hemisphere), memory formation (hippocampus)
Occipital	Back of the brain	Primary visual cortex (vision)

18.3 Localisation of Function

Motor cortex (frontal lobe): the body is mapped contralaterally (left motor cortex controls the right side of the body and vice versa) and with disproportionate representation -- areas requiring fine motor control (hands, face, tongue) have larger areas of the motor cortex devoted to them than areas requiring less precise control (trunk, legs).

Somatosensory cortex (parietal lobe): similarly organised contralaterally and with disproportionate representation (lips and fingertips have large areas).

Evidence for localisation of function comes from:

• Brain imaging (fMRI, PET scans): shows which brain areas are active during specific tasks.
• Electrical stimulation (during brain surgery): stimulating specific areas produces specific movements or sensations.
• Lesion studies (patients with brain damage): damage to Broca's area causes expressive aphasia (difficulty speaking); damage to Wernicke's area causes receptive aphasia (difficulty understanding speech).
• Animal experiments: ablation (surgical removal) of specific brain areas in animals and observation of resulting deficits.

18.4 Neuroplasticity

Neuroplasticity is the ability of the brain to change its structure and function in response to experience, learning, or injury. Mechanisms include:

• Synaptic plasticity: strengthening (LTP) or weakening (LTD) of synaptic connections based on activity.
• Synaptogenesis: formation of new synapses in response to learning.
• Axonal sprouting: surviving neurons grow new branches to replace connections lost to damage.
• Neurogenesis: production of new neurons in the hippocampus and olfactory bulb (limited in adult mammals).

Neuroplasticity is greatest during childhood (critical periods for language acquisition, vision development) but continues throughout life. It underlies learning, memory, and recovery from brain injury (e.g., stroke rehabilitation).

19. Visual Processing in Detail

19.1 Structure of the Eye

Component	Function
Cornea	Transparent outer layer; refracts (bends) light; provides most of the eye's focusing power
Iris	Coloured ring of muscle; controls the size of the pupil (regulates light entry)
Pupil	Hole in the iris; allows light to enter the eye
Lens	Transparent, flexible structure; fine-tunes focusing (accommodation) by changing shape
Retina	Light-sensitive layer at the back of the eye; contains photoreceptors (rods and cones)
Fovea	Area of the retina with the highest density of cones; provides the sharpest vision (highest visual acuity)
Optic nerve	Carries impulses from the retina to the brain
Blind spot (optic disc)	Where the optic nerve leaves the eye; no photoreceptors, so no vision at this point

19.2 Rods and Cones

Feature	Rods	Cones
Sensitivity	High (function well in low light)	Low (require bright light)
Visual acuity	Low (many rods share a single ganglion cell, so signals are pooled)	High (each cone connects to its own ganglion cell via a bipolar cell, so signals are separate)
Colour vision	No (only one type of rhodopsin pigment, maximally sensitive at $\approx 500\ \mathrm{nm}$)	Yes (three types: S-cones $\approx 420\ \mathrm{nm}$, M-cones $\approx 534\ \mathrm{nm}$, L-cones $\approx 564\ \mathrm{nm}$)
Distribution	Concentrated in the periphery of the retina; absent from the fovea	Concentrated in the fovea; sparse in the periphery
Response speed	Slow	Fast
Number	$\approx 120$ million per eye	$\approx 6$ million per eye

19.3 Phototransduction

In the dark, rod cells have high levels of cGMP, which opens $\mathrm{Na^+}$ channels (cGMP-gated channels). $\mathrm{Na^+}$ flows in, depolarising the cell to approximately $-40\ \mathrm{mV}$. This depolarisation causes the release of the neurotransmitter glutamate onto bipolar cells.

When light strikes rhodopsin, the retinal component changes from the 11-cis to the all-trans configuration. This activates transducin (a G-protein), which activates phosphodiesterase (PDE). PDE hydrolyses cGMP to GMP, reducing cGMP levels. The $\mathrm{Na^+}$ channels close, the cell hyperpolarises (to approximately $-70\ \mathrm{mV}$), and glutamate release is reduced.

This hyperpolarisation is unusual (most sensory receptors depolarise when stimulated) but effective: the reduction in glutamate causes the bipolar cells to change their activity, which is transmitted to ganglion cells and then to the brain via the optic nerve.

19.4 Accommodation

Accommodation is the process by which the lens changes shape to focus light from objects at different distances on the retina:

• Distant objects ($> 6\ \mathrm{m}$): the ciliary muscles are relaxed, the suspensory ligaments are taut, and the lens is pulled thin (flatter, lower refractive power).
• Near objects ($< 6\ \mathrm{m}$): the ciliary muscles contract, the suspensory ligaments slacken, and the elastic lens springs back to a more rounded shape (thicker, higher refractive power).

The near point is the closest distance at which the eye can focus (approximately 25 cm for a young adult). It increases with age as the lens becomes less elastic (presbyopia).

19.5 Colour Blindness

Colour blindness results from the absence or malfunction of one or more types of cone:

Type	Cause	Frequency
Protanopia	Missing L-cones (red)	1% of males
Deuteranopia	Missing M-cones (green)	1% of males
Tritanopia	Missing S-cones (blue)	Rare ($< 0.01\%$)
Red-green colour blindness	Missing or defective L-cones or M-cones	8% of males, 0.5% of females

Colour blindness is X-linked recessive (genes for L-cones and M-cones are on the X chromosome), which explains why it is much more common in males (who have only one X chromosome).

20. Neuronal Communication: Comparative Summary

20.1 Electrical vs Chemical Transmission

Feature	Electrical Synapse	Chemical Synapse
Gap junctions	Present (connexon channels)	Not present
Speed	Very fast (no synaptic delay)	Slower (synaptic delay $\approx 0.5\ \mathrm{ms}$)
Direction	Usually bidirectional	Unidirectional (presynaptic $\to$ postsynaptic)
Transmission	Direct ionic current flow	Neurotransmitter release and receptor binding
Modulation	Limited	Highly modifiable (basis of learning and memory)
Location	Cardiac muscle, smooth muscle, some neurons	Most neurons in the CNS and all at neuromuscular junctions

20.2 Synaptic Integration

A single neuron may receive thousands of synaptic inputs from other neurons. Whether the neuron fires an action potential depends on the sum of all inputs at the axon hillock:

• Excitatory postsynaptic potentials (EPSPs): depolarising (e.g., caused by glutamate, ACh).
• Inhibitory postsynaptic potentials (IPSPs): hyperpolarising (e.g., caused by GABA, glycine).
• Temporal summation: multiple EPSPs from the same synapse arriving in rapid succession combine to reach threshold.
• Spatial summation: EPSPs from multiple different synapses arriving simultaneously combine to reach threshold.

If the summed depolarisation at the axon hillock reaches the threshold potential (approximately $-55\ \mathrm{mV}$), voltage-gated $\mathrm{Na^+}$ channels open, and an action potential is initiated.

warning

Common Pitfall Students often confuse the terms "threshold" and "resting potential." The resting potential ($-70\ \mathrm{mV}$) is the membrane potential of an unstimulated neuron. The threshold potential ($-55\ \mathrm{mV}$) is the depolarisation level that must be reached to trigger an action potential. If the membrane depolarises to $-60\ \mathrm{mV}$ (above resting but below threshold), no action potential is fired.

25. Reflex Arcs: Detailed Mechanisms

25.1 Components of a Reflex Arc

1. Receptor: detects the stimulus and converts it to an electrical impulse (transduction).
2. Sensory neuron: transmits the impulse from the receptor to the CNS (spinal cord or brain).
3. Relay neuron (interneuron): connects the sensory neuron to the motor neuron within the CNS.
4. Motor neuron: transmits the impulse from the CNS to the effector.
5. Effector: carries out the response (muscle contracts or gland secretes).

25.2 The Spinal Reflex

A spinal reflex does not involve the brain (the neural pathway is confined to the spinal cord). This allows rapid, involuntary responses that protect the body from harm.

Example: The withdrawal reflex (pulling hand away from a hot object).

1. Heat receptors in the skin detect the stimulus.
2. A sensory neuron transmits the impulse to the spinal cord.
3. A relay neuron connects the sensory neuron to a motor neuron.
4. A motor neuron transmits the impulse to the biceps muscle (flexor) in the arm.
5. The biceps contracts, pulling the hand away from the hot object.

This is a monosynaptic reflex (only one synapse, between the sensory and motor neurons) or a polysynaptic reflex (at least one relay neuron and two synapses).

25.3 Reciprocal Innervation and Inhibition

When a muscle contracts during a reflex, the antagonistic muscle must relax. This is achieved by a reciprocal inhibitory interneuron, which releases an inhibitory neurotransmitter (glycine or GABA) onto the motor neuron supplying the antagonistic muscle, preventing it from contracting.

In the withdrawal reflex:

• The biceps (flexor) motor neuron is stimulated (excitatory synapse).
• The triceps (extensor) motor neuron is inhibited (inhibitory synapse).
• The biceps contracts and the triceps relaxes, allowing the arm to flex.

25.4 The Importance of Reflexes

Feature	Why It Matters
Speed	Reflexes are faster than voluntary responses because they involve fewer synapses and shorter neural pathways (no processing in the brain). This is critical for survival (e.g., pulling away from heat before tissue damage occurs).
Involuntary	Reflexes do not require conscious thought or decision-making, freeing the brain for other tasks.
Protection	Reflexes protect the body from harm (withdrawal, blink, cough, sneeze, gag).
Adaptation	Simple reflexes can be modified by learning (e.g., the vestibulo-ocular reflex, which stabilises gaze, can be adapted).

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tip

Diagnostic Test

24. Muscle Contraction: The Sliding Filament Theory

24.1 Structure of Skeletal Muscle

A muscle is made up of many muscle fibres (cells), each containing many myofibrils. Each myofibril is composed of repeating units called sarcomeres, the functional units of muscle contraction.

Each sarcomere contains two types of protein filament:

Filament	Protein	Structure	Function
Thick filaments	Myosin	Golf-club-shaped heads on a long tail; heads have ATPase activity and bind to actin	Pull thin filaments towards the centre of the sarcomere during contraction
Thin filaments	Actin (plus troponin and tropomyosin)	Helical chain of actin monomers with troponin-tropomyosin complex	Slides past thick filaments during contraction

Bands and lines in a sarcomere:

Region	Appearance	What It Contains
Z line (Z disc)	Dark line at each end of the sarcomere	Anchors the thin filaments
I band	Light band	Thin filaments only (shortens during contraction)
A band	Dark band	Full length of thick filaments (stays the same length during contraction)
H zone	Lighter region in the centre of the A band	Thick filaments only (shortens during contraction)
M line	Dark line in the centre of the H zone	Anchors the thick filaments

24.2 The Sliding Filament Mechanism

1. Resting state: tropomyosin blocks the myosin-binding sites on actin. The myosin head is in the "cocked" position, with ADP and Pi bound.
2. Calcium ions released: action potential triggers $\mathrm{Ca^{2+}}$ release from the sarcoplasmic reticulum. $\mathrm{Ca^{2+}}$ binds to troponin C, causing a conformational change that moves tropomyosin away from the myosin-binding sites on actin.
3. Cross-bridge formation: the myosin head binds to an exposed binding site on actin, forming a cross-bridge.
4. Power stroke: the myosin head pivots, pulling the thin filament towards the centre of the sarcomere. ADP and Pi are released during the power stroke.
5. ATP binding: a new ATP molecule binds to the myosin head, causing it to detach from actin.
6. ATP hydrolysis: the ATP is hydrolysed to ADP and Pi, and the energy released recocks the myosin head to its starting position. The cycle is ready to repeat.

Each cycle moves the thin filament approximately 5 nm past the thick filament. Thousands of cross-bridge cycles occur simultaneously in each sarcomere, producing the macroscopic contraction of the muscle.

24.3 Energy for Muscle Contraction

ATP is required for:

• The power stroke (myosin ATPase activity).
• Detaching myosin from actin (preventing rigor mortis).
• Pumping $\mathrm{Ca^{2+}}$ back into the sarcoplasmic reticulum (by $\mathrm{Ca^{2+}}$-ATPase, terminating contraction).
• Active transport of $\mathrm{Na^+}$ and $\mathrm{K^+}$ by the $\mathrm{Na^+/K^+}$ ATPase (maintaining resting membrane potential for the next action potential).

ATP is regenerated by:

• Aerobic respiration (during rest and light exercise): glucose and fatty acids are oxidised in mitochondria.
• Anaerobic respiration (during intense exercise): glucose is converted to lactate, providing rapid ATP but limited quantity.
• Creatine phosphate: a short-term energy store in muscle cells. Creatine phosphate donates a phosphate group to ADP via creatine kinase, rapidly regenerating ATP:

$\text{Creatine phosphate} + \text{ADP} \rightleftharpoons \text{Creatine} + \text{ATP}$

This provides approximately 5--10 seconds of maximal ATP supply before anaerobic glycolysis becomes the dominant source.

24.4 Slow-Twitch and Fast-Twitch Muscle Fibres

Feature	Type I (Slow-Twitch)	Type IIb (Fast-Twitch)
Colour	Red (high myoglobin content)	White (low myoglobin)
Energy source	Aerobic respiration (fat and glucose)	Anaerobic glycolysis (glycogen)
Mitochondria	Many	Few
Capillary supply	Dense	Sparse
Contraction speed	Slow	Fast
Force generated	Low	High
Fatigue resistance	High (resistant to fatigue)	Low (fatigues quickly)
Use	Endurance activities (marathon running, posture)	Short bursts of power (sprinting, weightlifting)

Most muscles contain a mixture of both fibre types. The proportion is genetically determined but can be modified to some extent by training (endurance training increases the oxidative capacity of Type II fibres).

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tip

Diagnostic Test

21. Synaptic Transmission: Detailed Mechanism

21.1 Step-by-Step: Cholinergic Synapse

1. Action potential arrives at the presynaptic terminal (axion terminal).
2. Depolarisation of the presynaptic membrane opens voltage-gated calcium channels.
3. $\mathrm{Ca^{2+}}$ ions flow in down their electrochemical gradient (high concentration outside, negative membrane potential inside).
4. The increase in intracellular $\mathrm{Ca^{2+}}$ causes synaptic vesicles (containing the neurotransmitter acetylcholine, ACh) to move to and fuse with the presynaptic membrane.
5. ACh is released into the synaptic cleft by exocytosis.
6. ACh diffuses across the synaptic cleft (gap of approximately 20--40 nm) and binds to nicotinic ACh receptors on the postsynaptic membrane.
7. These receptors are ligand-gated sodium channels. When ACh binds, the channel opens, allowing $\mathrm{Na^+}$ to flow into the postsynaptic cell.
8. This causes depolarisation of the postsynaptic membrane (an excitatory postsynaptic potential, EPSP).
9. If sufficient EPSPs summate to reach threshold at the axon hillock, an action potential is initiated in the postsynaptic neuron.
10. ACh is rapidly broken down by the enzyme acetylcholinesterase (attached to the postsynaptic membrane), terminating the signal. The products (choline and acetate) are taken up by the presynaptic terminal and used to resynthesise ACh.

21.2 Synaptic Transmission: Quantitative Analysis

Synaptic delay: the time between the arrival of the action potential at the presynaptic terminal and the initiation of the postsynaptic potential is approximately 0.5 ms. This delay is due to the time taken for:

• $\mathrm{Ca^{2+}}$ influx.
• Vesicle fusion and neurotransmitter release.
• Diffusion across the synaptic cleft.
• Receptor binding and channel opening.

In a pathway with many synapses (e.g., a polysynaptic reflex arc with 3 synapses), the total delay is approximately $3 \times 0.5 = 1.5\ \mathrm{ms}$ plus the conduction time along the axons.

Temporal summation: if a single presynaptic neuron fires at a high frequency (e.g., 100 impulses per second, or one every 10 ms), the EPSPs overlap and summate because each EPSP lasts approximately 10--20 ms before decaying.

Spatial summation: if multiple presynaptic neurons fire simultaneously, their EPSPs add together at the postsynaptic membrane.

Worked Example. A single EPSP depolarises the postsynaptic membrane by $5\ \mathrm{mV}$. The threshold for an action potential is $-55\ \mathrm{mV}$, and the resting potential is $-70\ \mathrm{mV}$. The membrane needs to be depolarised by $15\ \mathrm{mV}$ to reach threshold.

• Temporal summation: at least 3 rapid EPSPs from a single presynaptic neuron ($3 \times 5 = 15\ \mathrm{mV}$).
• Spatial summation: at least 3 simultaneous EPSPs from 3 different presynaptic neurons ($3 \times 5 = 15\ \mathrm{mV}$).
• Combination: 2 EPSPs from neuron A + 1 EPSP from neuron B ($10 + 5 = 15\ \mathrm{mV}$).

22. The Nervous System and Disease

22.1 Parkinson's Disease

Cause: degeneration of dopamine-producing neurons in the substantia nigra (midbrain). Dopamine is essential for the smooth initiation and coordination of voluntary movement.

Symptoms: resting tremor (pill-rolling tremor of the hands), bradykinesia (slowness of movement), rigidity (stiff muscles), postural instability.

Mechanism: the basal ganglia (a group of deep brain nuclei) require a balance between dopamine (inhibitory) and acetylcholine (excitatory) for normal motor control. Loss of dopamine creates an imbalance, resulting in excessive cholinergic activity and the characteristic motor symptoms.

Treatment:

• L-DOPA (levodopa): a dopamine precursor that can cross the blood-brain barrier (dopamine itself cannot). L-DOPA is converted to dopamine in the brain by DOPA decarboxylase. Often given with carbidopa (a DOPA decarboxylase inhibitor that does not cross the blood-brain barrier) to prevent peripheral conversion.
• Dopamine agonists (e.g., bromocriptine): mimic dopamine by directly stimulating dopamine receptors.
• Anticholinergics: reduce the excessive cholinergic activity.
• Deep brain stimulation: electrodes implanted in the subthalamic nucleus deliver electrical impulses, reducing tremor and rigidity.

22.2 Myasthenia Gravis

Cause: autoimmune disease in which antibodies are produced against nicotinic ACh receptors on the postsynaptic membrane of the neuromuscular junction. The antibodies block the receptors, causing their internalisation and degradation, and activate complement, damaging the postsynaptic membrane.

Effect: fewer functional ACh receptors are available. Although ACh is released normally, the postsynaptic response is reduced. The end-plate potential may be too small to reach threshold, and the action potential fails to fire in the muscle fibre. This causes muscle weakness that worsens with repeated use (fatigability).

Symptoms: drooping eyelids (ptosis), double vision (diplopia), difficulty swallowing and speaking, weakness in the limbs.

Treatment: acetylcholinesterase inhibitors (e.g., pyridostigmine) increase the concentration of ACh in the synaptic cleft by preventing its breakdown, allowing more ACh molecules to bind to the remaining receptors and increasing the probability of reaching threshold.

22.3 Multiple Sclerosis

Cause: autoimmune disease in which T cells and macrophages attack the myelin sheath surrounding neurons in the central nervous system. The myelin is replaced by scar tissue (sclerosis, plaques), disrupting saltatory conduction.

Effect: action potentials are slowed or blocked because:

• The myelin sheath provides electrical insulation, allowing the action potential to "jump" between Nodes of Ranvier (saltatory conduction).
• Loss of myelin exposes the axon membrane, increasing the capacitance and decreasing the membrane resistance, so current leaks away instead of flowing to the next node.
• The action potential may fail to reach the next Node of Ranvier (conduction block).

Symptoms: fatigue, visual disturbances (optic neuritis), numbness, muscle weakness, tremor, difficulty with coordination and balance.

Type of MS:

Type	Description
Relapsing-remitting (RRMS)	Episodes of worsening symptoms (relapses) followed by periods of improvement (remissions)
Secondary progressive (SPMS)	Initial relapsing-remitting course followed by progressive worsening without remissions
Primary progressive (PPMS)	Gradual worsening from onset without relapses

23. Sensory Receptors

23.1 Types of Sensory Receptors

Receptor Type	Stimulus	Location	Example
Mechanoreceptor	Mechanical deformation (pressure, stretch, vibration)	Skin, inner ear, muscles	Pacinian corpuscle, hair cells in cochlea
Thermoreceptor	Temperature change	Skin, hypothalamus	Warm and cold receptors in dermis
Chemoreceptor	Chemical concentration ($\mathrm{O_2}$, $\mathrm{CO_2}$, glucose, pH)	Carotid body, aortic body, taste buds, olfactory epithelium	Carotid body (detects blood $p\mathrm{CO_2}$)
Photoreceptor	Light intensity (rods) and wavelength (cones)	Retina	Rods and cones
Baroreceptor	Blood pressure change	Aortic arch, carotid sinus	Aortic baroreceptors

23.2 The Pacinian Corpuscle: Mechanism

The Pacinian corpuscle is a pressure receptor found in the skin, tendons, and ligaments. It consists of a sensory nerve ending surrounded by concentric layers of connective tissue (lamellae).

1. Pressure deforms the corpuscle, stretching the lamellae.
2. The stretching deforms the nerve ending, opening stretch-mediated sodium channels in the membrane.
3. $\mathrm{Na^+}$ flows into the nerve ending, causing depolarisation (a generator potential).
4. If the generator potential reaches threshold, it triggers an action potential in the sensory neuron.
5. The action potential is transmitted along the sensory neuron to the CNS.
6. The action potential frequency (rate of firing) is proportional to the intensity of the stimulus (stronger pressure $=$ larger generator potential $=$ higher frequency of action potentials).

23.3 Adaptation

Some receptors adapt (respond less to a continued stimulus):

• Phasic (rapidly adapting) receptors: respond strongly at the onset of a stimulus but quickly reduce their firing rate. They detect changes (dynamic stimuli). Example: Pacinian corpuscle (detects vibration and changes in pressure, not sustained pressure).
• Tonic (slowly adapting) receptors: maintain their firing rate as long as the stimulus is present. They detect steady-state stimuli. Example: stretch receptors in muscles (muscle spindles), thermoreceptors.

24. The Brain: Structure and Function in Detail

24.1 Major Brain Regions

Region	Location	Key Functions
Cerebral cortex	Outer layer of cerebrum	Conscious thought, language, memory, decision-making, sensory processing, voluntary movement
Cerebellum	Behind brainstem, below cerebrum	Coordination of movement, balance, posture, motor learning
Hypothalamus	Below thalamus	Thermoregulation, osmoregulation, hunger/thirst, sleep-wake cycle, endocrine control (via pituitary)
Medulla oblongata	Lowest part of brainstem	Control of breathing rate, heart rate, blood pressure (autonomic functions)
Corpus callosum	Band of nerve fibres connecting the two cerebral hemispheres	Communication between left and right hemispheres
Thalamus	Centre of brain, above hypothalamus	Relay station for sensory information (except olfaction) to the cerebral cortex

24.2 Cerebral Hemispheres and Lateralisation

The cerebral cortex is divided into two hemispheres, each with four lobes:

Lobe	Location	Primary Functions
Frontal	Behind forehead	Motor control (primary motor cortex), decision-making, planning, personality, speech production (Broca's area, usually in left hemisphere)
Parietal	Behind frontal lobe	Somatosensory processing (primary somatosensory cortex), spatial awareness
Temporal	Below frontal and parietal lobes	Auditory processing (primary auditory cortex), memory (hippocampus), language comprehension (Wernicke's area, usually in left hemisphere)
Occipital	Back of brain	Visual processing (primary visual cortex)

Lateralisation: certain functions are predominantly processed in one hemisphere:

• Left hemisphere (in most right-handed people): language (speech and comprehension), logical reasoning, mathematical ability.
• Right hemisphere: spatial awareness, face recognition, musical ability, creative thinking.

24.3 Memory Formation

Memory involves three stages:

1. Encoding: converting sensory information into a form that can be stored. Involves the hippocampus (for declarative memories -- facts and events) and amygdala (for emotional memories).
2. Storage: maintaining the encoded information. Short-term memory (working memory) is stored in the prefrontal cortex and lasts seconds to minutes. Long-term memory is stored in various cortical areas and can last a lifetime.
3. Retrieval: accessing stored information when needed.

Long-term potentiation (LTP): a persistent strengthening of synaptic connections that underlies learning and memory. When two neurons are repeatedly activated together, the synaptic connection between them is strengthened (Hebb's rule: "neurons that fire together, wire together"). LTP involves:

• Increased release of neurotransmitter (glutamate) from the presynaptic neuron.
• Insertion of additional AMPA receptors into the postsynaptic membrane.
• Activation of NMDA receptors, which allows $\mathrm{Ca^{2+}}$ entry, triggering intracellular signalling cascades that lead to structural changes at the synapse.

25. Neurodegenerative Diseases

25.1 Parkinson's Disease

• Cause: degeneration of dopamine-producing neurons in the substantia nigra (midbrain), leading to reduced dopamine in the basal ganglia.
• Symptoms: tremor (especially at rest), bradykinesia (slowness of movement), rigidity, postural instability.
• Treatment: L-DOPA (precursor to dopamine; crosses the blood-brain barrier; converted to dopamine in the brain). Deep brain stimulation (electrodes implanted in the subthalamic nucleus to modulate neural activity).
• Limitations of L-DOPA: does not stop disease progression; side effects include dyskinesia (involuntary movements) after prolonged use.

25.2 Alzheimer's Disease

• Cause: accumulation of amyloid-$\beta$ plaques (extracellular protein deposits) and neurofibrillary tangles (intracellular tau protein aggregates) in the brain, leading to neuronal death and brain atrophy.
• Symptoms: progressive memory loss, confusion, language difficulties, personality changes, loss of ability to perform daily activities.
• Risk factors: age (greatest risk factor), APOE4 allele (genetic), head injury, cardiovascular disease.
• Treatment: acetylcholinesterase inhibitors (donepezil, rivastigmine) to increase acetylcholine levels; memantine (NMDA receptor antagonist) to reduce excitotoxicity. Neither cures the disease; they slow symptom progression.

25.3 Motor Neurone Disease (MND / ALS)

• Cause: progressive degeneration of upper and lower motor neurons.
• Symptoms: progressive muscle weakness and wasting; difficulty speaking, swallowing, and breathing; eventually fatal (usually within 3--5 years of diagnosis).
• Treatment: riluzole (slows disease progression by reducing glutamate release); supportive care (ventilation, feeding tubes).

26. Synaptic Transmission: Detailed Mechanisms

26.1 Excitatory and Inhibitory Postsynaptic Potentials (EPSPs and IPSPs)

Feature	EPSP	IPSP
Neurotransmitter	Glutamate (main excitatory NT in CNS)	GABA (main inhibitory NT in CNS) or glycine (in spinal cord)
Ion channels opened	$\mathrm{Na^+}$ (and some $\mathrm{Ca^{2+}}$)	$\mathrm{Cl^-}$ (and sometimes $\mathrm{K^+}$)
Ion movement	$\mathrm{Na^+}$ flows in (depolarisation)	$\mathrm{Cl^-}$ flows in (hyperpolarisation)
Effect on membrane potential	Moves towards threshold (closer to $-55\ \mathrm{mV}$)	Moves further from threshold (more negative, e.g., $-75\ \mathrm{mV}$)
Effect on likelihood of action potential	Increases (more likely to fire)	Decreases (less likely to fire)

Spatial summation: multiple EPSPs from different presynaptic neurons arrive at the same postsynaptic neuron simultaneously, adding together to reach threshold.

Temporal summation: multiple EPSPs from a single presynaptic neuron arrive in rapid succession (before the previous EPSP has decayed), adding together to reach threshold.

26.2 Neurotransmitter Inactivation

Neurotransmitters must be rapidly removed from the synaptic cleft to allow precise signalling:

Mechanism	Example	Notes
Diffusion	Any NT	NT diffuses away from the synapse; slow and non-specific
Enzymatic degradation	Acetylcholinesterase (AChE) breaks down ACh into choline and acetate; MAO breaks down noradrenaline	AChE inhibitors (e.g., organophosphorus nerve agents, sarin) cause ACh accumulation, leading to muscle paralysis and death. Edrophoton (a reversible AChE inhibitor) is used to diagnose myasthenia gravis
Reuptake	SERT reuptakes serotonin; DAT reuptakes dopamine; NET reuptakes noradrenaline	SSRIs (selective serotonin reuptake inhibitors) block SERT, increasing serotonin in the synaptic cleft (used to treat depression)

26.3 Drugs and the Nervous System

Drug	Target	Mechanism	Effect
Nicotine	Nicotinic ACh receptors (excitatory)	Agonist: binds to and activates the receptor	Stimulates the release of dopamine in the reward pathway; causes addiction
Curare	Nicotinic ACh receptors at neuromuscular junction	Competitive antagonist: blocks ACh binding	Muscle paralysis (used historically as arrow poison; modern derivative vecuronium used in surgery)
Benzodiazepines (e.g., diazepam)	GABA_A receptors	Positive allosteric modulator: enhances GABA binding, increasing $\mathrm{Cl^-}$ influx	Anxiolytic, sedative, anticonvulsant
Cocaine	Dopamine transporter (DAT)	Blocks reuptake of dopamine	Increased dopamine in synaptic cleft; euphoria and addiction
Propranolol	$\beta$-adrenergic receptors	Antagonist: blocks noradrenaline binding	Reduces heart rate and blood pressure (used to treat hypertension, anxiety)
Lidocaine	Voltage-gated $\mathrm{Na^+}$ channels	Blocks channels, preventing action potential initiation	Local anaesthetic

26.4 Myasthenia Gravis: An Autoimmune Disease

• Cause: autoantibodies against nicotinic ACh receptors at the neuromuscular junction.
• Effect: reduced number of functional ACh receptors; fewer ACh receptors can be activated, so end-plate potentials are smaller and may not reach threshold.
• Symptoms: muscle weakness and fatigue (worse with repeated use, improves with rest); ptosis (drooping eyelids); difficulty swallowing and speaking; respiratory muscle weakness (can be fatal).
• Treatment: acetylcholinesterase inhibitors (e.g., pyridostigmine) to increase ACh availability; immunosuppressants (e.g., corticosteroids); thymectomy (thymus often abnormal in MG patients).

27. The Endocrine System: Detailed Overview

27.1 Major Endocrine Glands and Hormones

Gland	Hormone(s)	Target	Function
Hypothalamus	Releasing and inhibiting hormones (e.g., GnRH, TRH, CRH, GHRH, somatostatin)	Anterior pituitary	Controls anterior pituitary hormone secretion
Posterior pituitary	ADH (vasopressin), oxytocin	Kidneys (ADH); uterus/breasts (oxytocin)	ADH: water reabsorption. Oxytocin: uterine contraction, milk ejection
Anterior pituitary	FSH, LH, ACTH, TSH, GH, prolactin	Various	FSH/LH: reproduction. ACTH: adrenal cortex. TSH: thyroid. GH: growth. Prolactin: milk production
Thyroid	Thyroxine ($\mathrm{T_4}$), triiodothyronine ($\mathrm{T_3}$), calcitonin	Most body cells (thyroid hormones); bones (calcitonin)	Increases metabolic rate; promotes growth and development; calcitonin lowers blood $\mathrm{Ca^{2+}}$
Parathyroid	PTH (parathyroid hormone)	Bones, kidneys, intestine	Raises blood $\mathrm{Ca^{2+}}$ (stimulates osteoclasts; increases $\mathrm{Ca^{2+}}$ reabsorption in kidneys)
Adrenal cortex	Aldosterone, cortisol, androgens	Kidneys (aldosterone); most cells (cortisol)	Aldosterone: $\mathrm{Na^+}$ reabsorption. Cortisol: stress response, anti-inflammatory
Pancreas (islets)	Insulin ($\beta$ cells), glucagon ($\alpha$ cells)	Liver, muscle, adipose	Regulates blood glucose
Ovaries	Oestrogen, progesterone	Uterus, breasts, hypothalamus	Female secondary sexual characteristics; regulates menstrual cycle; maintains pregnancy
Testes	Testosterone	Various	Male secondary sexual characteristics; spermatogenesis; muscle and bone growth

27.2 Hormone Action: Signal Transduction

Hormones bind to specific receptors on (or in) target cells. The type of receptor determines the mechanism of action:

Receptor Type	Hormone Type	Mechanism	Speed
Intracellular (nuclear)	Steroid hormones (testosterone, oestrogen, cortisol), thyroid hormones	Hormone diffuses through the membrane; binds to intracellular receptor; hormone-receptor complex enters nucleus; acts as a transcription factor, directly affecting gene expression	Slow (hours to days)
Cell surface (GPCR)	Peptide hormones (insulin, glucagon, ADH), adrenaline	Hormone binds to G-protein coupled receptor; activates second messenger cascade (cAMP, $\mathrm{IP_3/DAG}$, $\mathrm{Ca^{2+}}$); amplifies signal	Fast (seconds to minutes)
Cell surface (tyrosine kinase)	Insulin, growth factors	Hormone binds to receptor tyrosine kinase; autophosphorylation; activates intracellular signalling cascade (MAPK, PI3K)	Minutes to hours

27.3 Second Messengers

Second Messenger	Generated By	Activated By	Effect
cAMP	Adenylate cyclase	G-protein ($\mathrm{G_s}$)	Activates protein kinase A (PKA), which phosphorylates target proteins
$\mathrm{IP_3}$	Phospholipase C (PLC)	G-protein ($\mathrm{G_q}$)	Binds to receptors on ER, releasing stored $\mathrm{Ca^{2+}}$
DAG	PLC	G-protein ($\mathrm{G_q}$)	Activates protein kinase C (PKC), which phosphorylates target proteins
$\mathrm{Ca^{2+}}$	Released from ER via $\mathrm{IP_3}$ receptors	$\mathrm{IP_3}$	Binds to calmodulin; $\mathrm{Ca^{2+}}$-calmodulin complex activates various enzymes

28. Visual Processing and the Eye

28.1 Structure of the Eye

Structure	Function
Cornea	Transparent front of the eye; refracts (bends) light; provides approximately 2/3 of the eye's total refractive power
Iris	Controls the size of the pupil (regulates light entry); contains circular and radial muscles
Pupil	Hole in the centre of the iris; allows light to enter the eye
Lens	Transparent, elastic structure; changes shape (accommodation) to focus light on the retina; controlled by ciliary muscles and suspensory ligaments
Retina	Light-sensitive layer at the back of the eye; contains photoreceptors (rods and cones) and interneurons (bipolar cells, ganglion cells)
Fovea	Region of the retina with the highest visual acuity; densely packed with cones; no rods
Optic nerve	Carries action potentials from ganglion cells to the brain
Blind spot	Where the optic nerve exits the eye; no photoreceptors

28.2 Accommodation (Focusing)

Condition	Distant Object (> 6 m)	Near Object (< 6 m)
Ciliary muscles	Relaxed	Contracted (constrict)
Suspensory ligaments	Taut (pulled tight)	Slack (loose)
Lens shape	Thin, flattened (weakly refracting)	Fat, rounded (strongly refracting)

28.3 Rods vs Cones

Feature	Rods	Cones
Pigment	Rhodopsin	Photopsin (three types: S, M, L -- sensitive to blue, green, red)
Sensitivity	Very sensitive to low light	Less sensitive; require brighter light
Colour vision	No (monochromatic)	Yes (trichromatic colour vision)
Visual acuity	Low (many rods share one bipolar cell; convergence)	High (one cone connects to one bipolar cell; 1:1 pathway)
Distribution	Concentrated in the periphery of the retina	Concentrated in the fovea
Number	~120 million per eye	~6 million per eye
Response time	Slow	Fast
Function	Night vision; peripheral vision	Daytime vision; colour vision; fine detail

28.4 Control of Heart Rate

The autonomic nervous system controls heart rate:

Factor	Detected By	Response	Pathway
High blood pressure	Baroreceptors in aortic arch and carotid sinus	Decrease heart rate	Baroreceptors $\to$ sensory neurone $\to$ medulla oblongata (cardiovascular centre) $\to$ parasympathetic (vagus nerve) $\to$ SAN: slows heart rate
Low blood pressure	Baroreceptors	Increase heart rate	Baroreceptors $\to$ medulla $\to$ sympathetic nervous system $\to$ SAN: increases heart rate; adrenaline also increases heart rate
High blood $\mathrm{CO_2}$ / low $\mathrm{O_2}$ / low pH	Chemoreceptors in aortic and carotid bodies	Increase heart rate and breathing rate	Chemoreceptors $\to$ medulla $\to$ sympathetic nervous system + increased ventilation rate

29. Muscle Contraction: The Sliding Filament Mechanism

29.1 Structure of Skeletal Muscle

Structure	Description
Muscle fascicle	Bundle of muscle fibres, surrounded by perimysium
Muscle fibre (cell)	Multinucleate cell (formed by fusion of myoblasts); contains many myofibrils
Myofibril	Contractile unit; composed of repeating sarcomeres
Sarcomere	Functional unit of muscle contraction; from Z-line to Z-line
Thin filaments (actin)	Made of actin (with binding sites for myosin heads), tropomyosin (covers binding sites at rest), and troponin (binds $\mathrm{Ca^{2+}}$)
Thick filaments (myosin)	Made of myosin, with globular heads that bind to actin and hydrolyse ATP

29.2 The Sliding Filament Mechanism

1. Action potential arrives at the neuromuscular junction, triggering release of ACh.
2. Action potential spreads along the sarcolemma (muscle cell membrane) and down T-tubules (infoldings of the sarcolemma).
3. $\mathrm{Ca^{2+}}$ release: the action potential triggers opening of $\mathrm{Ca^{2+}}$ release channels (ryanodine receptors) on the sarcoplasmic reticulum, releasing $\mathrm{Ca^{2+}}$ into the sarcoplasm.
4. $\mathrm{Ca^{2+}}$ binds to troponin, causing a conformational change that moves tropomyosin away from the myosin-binding sites on actin.
5. Cross-bridge formation: myosin heads bind to exposed binding sites on actin, forming cross-bridges.
6. Power stroke: the myosin heads pivot, pulling the thin filaments towards the centre of the sarcomere (the H-zone and I-band shorten; the A-band remains the same length).
7. ATP binds to myosin, causing the myosin head to detach from actin.
8. ATP hydrolysis: the myosin head is re-cocked (returns to its original position), ready for another cycle.
9. $\mathrm{Ca^{2+}}$ is pumped back into the sarcoplasmic reticulum by $\mathrm{Ca^{2+}}$-ATPase pumps (active transport), tropomyosin re-covers binding sites, and the muscle relaxes.

29.3 Energy for Muscle Contraction

Source	Duration	Capacity	Use
Phosphocreatine (PCr)	0--10 s	Very limited	Sprinting; weightlifting (maximal effort)
Anaerobic glycolysis	10 s -- 3 min	Limited; produces lactate	400 m sprint; intense exercise
Aerobic respiration	> 3 min	Virtually unlimited (fat stores)	Marathon; endurance exercise

29.4 Fast vs Slow Muscle Fibres

Feature	Type I (Slow-Twitch)	Type IIb (Fast-Twitch)
Contraction speed	Slow	Fast
Myosin ATPase activity	Low	High
Fatigue resistance	High (resistant to fatigue)	Low (fatigue quickly)
Mitochondrial density	High	Low
Myoglobin concentration	High (red muscle)	Low (white muscle)
Glycogen stores	Low	High
$\mathrm{O_2}$ supply	High (many capillaries)	Low (fewer capillaries)
Energy source	Aerobic (fatty acids)	Anaerobic (glycogen)
Function	Endurance activities (posture, walking)	Explosive activities (sprinting, jumping)

30. Reflex Arcs and Instinctive Behaviour

30.1 Components of a Reflex Arc

A reflex arc is the pathway taken by nerve impulses in an automatic, involuntary response (reflex):

1. Stimulus: a change in the environment detected by a receptor.
2. Receptor: converts the stimulus into an electrical impulse (generator potential $\to$ action potential).
3. Sensory neurone: transmits the impulse from the receptor to the CNS (spinal cord or brain).
4. Relay neurone (interneuron): connects the sensory neurone to the motor neurone in the CNS (may also connect to the brain for conscious awareness).
5. Motor neurone: transmits the impulse from the CNS to the effector.
6. Effector: carries out the response (muscle contracts or gland secretes).

30.2 Types of Reflex

Type	Description	Example
Spinal reflex	Reflex arc passes through the spinal cord only (not the brain); very fast	Withdrawal reflex (pulling hand away from hot object); stretch reflex (knee jerk)
Cranial reflex	Reflex arc passes through the brain	Pupillary reflex (pupil constricts in bright light); blinking reflex
Simple reflex	Involves only one synapse (monosynaptic)	Knee jerk (patellar tendon) reflex
Conditioned reflex	A learned response to a stimulus that normally would not produce the response (classical conditioning)	Pavlov's dogs (salivating at the sound of a bell)

30.3 The Withdrawal Reflex

When the hand touches a hot object:

1. Heat receptors in the skin detect the stimulus and generate nerve impulses.
2. Sensory neurones transmit impulses to the spinal cord.
3. In the spinal cord, the sensory neurone synapses with:
   • A relay neurone (which transmits impulses to the brain -- the brain becomes aware of the pain after the reflex has occurred).
   • A motor neurone (which transmits impulses to the biceps muscle in the upper arm).
4. The biceps muscle contracts (flexor), pulling the hand away from the hot object.
5. Simultaneously, a relay neurone synapses with an inhibitory interneurone that inhibits the motor neurone to the triceps (extensor). This is reciprocal inhibition: the antagonist muscle is inhibited to prevent conflicting movements.

30.4 Control of Breathing Rate

Breathing rate is controlled by the medulla oblongata:

Factor	Detected By	Response
High blood $\mathrm{CO_2}$ ($p\mathrm{CO_2}$)	Chemoreceptors in aortic and carotid bodies; central chemoreceptors in medulla	Increase breathing rate and depth (hyperventilation)
Low blood $\mathrm{O_2}$ ($p\mathrm{O_2}$)	Peripheral chemoreceptors (carotid and aortic bodies)	Increase breathing rate (only significant when $p\mathrm{O_2}$ is very low; $\mathrm{CO_2}$ is normally the main stimulus)
Low blood pH	Central chemoreceptors (respond to $\mathrm{H^+}$ in cerebrospinal fluid; $\mathrm{CO_2}$ diffuses across blood-brain barrier and forms $\mathrm{H^+}$ via carbonic anhydrase)	Increase breathing rate

31. Habituation, Conditioning, and Learning

31.1 Habituation

Habituation is the simplest form of learning: an animal learns to ignore a repeated, harmless stimulus.

Example: a sea anemone withdraws its tentacles when first touched, but after repeated harmless touches, it no longer responds.

Biological importance: prevents the animal from wasting energy on responses to irrelevant stimuli; allows the nervous system to focus on genuinely important stimuli.

31.2 Classical Conditioning (Pavlovian Conditioning)

An animal learns to associate a new stimulus with an existing reflex response.

Example (Pavlov's dogs):

1. Unconditioned stimulus (US): food (naturally causes salivation).
2. Unconditioned response (UR): salivation.
3. Conditioned stimulus (CS): bell (initially does not cause salivation).
4. After repeated pairing of CS with US, the CS alone triggers the conditioned response (CR): salivation.

31.3 Operant Conditioning (Skinner)

An animal learns to associate a behaviour with a consequence (reward or punishment).

Type	Consequence	Effect on Behaviour	Example
Positive reinforcement	Reward (food, pleasure)	Behaviour increases	Rat presses lever to receive food pellet
Negative reinforcement	Removal of unpleasant stimulus	Behaviour increases	Pressing a button stops an electric shock
Positive punishment	Unpleasant stimulus applied	Behaviour decreases	Electric shock for wrong response
Negative punishment	Pleasant stimulus removed	Behaviour decreases	Toy taken away for bad behaviour

31.4 Insight Learning

The most complex form of learning: the animal solves a problem suddenly (without trial and error) by mentally manipulating concepts.

Example: a chimpanzee cannot reach a banana with a stick; it suddenly stacks boxes to reach the banana. This requires understanding cause-and-effect relationships.

32. Neuronal Communication: Worked Calculations

32.1 Resting Membrane Potential

The resting membrane potential is approximately $-70\ \mathrm{mV}$ (inside negative relative to outside). This is maintained by:

1. The $\mathrm{Na^+/K^+}$ ATPase (3 $\mathrm{Na^+}$ out, 2 $\mathrm{K^+}$ in).
2. Membrane permeability: at rest, the membrane is approximately 50--100 times more permeable to $\mathrm{K^+}$ than to $\mathrm{Na^+}$ (more $\mathrm{K^+}$ leak channels than $\mathrm{Na^+}$ leak channels).
3. $\mathrm{K^+}$ diffuses out of the cell down its concentration gradient, carrying positive charge with it, making the inside negative.

Nernst equation (simplified for one ion):

$E = \frac{RT}{zF} \ln \frac◆LB◆[\text{ion}]_{\text{out}}◆RB◆◆LB◆[\text{ion}]_{\text{in}}◆RB◆$

For $\mathrm{K^+}$: $E_K \approx -90\ \mathrm{mV}$; for $\mathrm{Na^+}$: $E_{Na} \approx +60\ \mathrm{mV}$.

The resting potential ($-70\ \mathrm{mV}$) is closer to $E_K$ than to $E_{Na}$, reflecting the greater permeability to $\mathrm{K^+}$.

32.2 Action Potential Phases

Phase	Membrane Potential	Ion Movements
Resting	$-70\ \mathrm{mV}$	$\mathrm{Na^+}$ and $\mathrm{K^+}$ leak channels open (net: $\mathrm{K^+}$ out)
Depolarisation	Rises to $+40\ \mathrm{mV}$	Voltage-gated $\mathrm{Na^+}$ channels open; $\mathrm{Na^+}$ rushes in
Peak	$+40\ \mathrm{mV}$	$\mathrm{Na^+}$ channels close (inactivated); $\mathrm{K^+}$ channels begin to open
Repolarisation	Falls back towards $-70\ \mathrm{mV}$	Voltage-gated $\mathrm{K^+}$ channels open; $\mathrm{K^+}$ rushes out
Hyperpolarisation	Briefly more negative than $-70\ \mathrm{mV}$	$\mathrm{K^+}$ channels close slowly; excess $\mathrm{K^+}$ efflux
Refractory period	Returns to $-70\ \mathrm{mV}$	$\mathrm{Na^+}$ channels are inactivated (absolute refractory period: no new action potential can be generated); then return to resting state (relative refractory period: only a larger stimulus can trigger a new action potential)

32.3 Speed of Nerve Impulse Conduction

The speed of conduction depends on:

Factor	Effect	Mechanism
Axon diameter	Larger diameter = faster conduction	Less resistance to current flow
Myelination	Myelinated axons conduct faster	Saltatory conduction: action potentials jump between nodes of Ranvier (gaps in the myelin sheath) rather than propagating along the entire axon membrane
Temperature	Higher temperature = faster conduction	Increases rate of ion channel opening and diffusion

Speeds:

• Unmyelinated axon ($0.5\ \mu\mathrm{m}$ diameter): approximately $0.5\ \mathrm{m\ s^{-1}}$
• Myelinated axon ($10\ \mu\mathrm{m}$ diameter): approximately $100\ \mathrm{m\ s^{-1}}$
• Squid giant axon ($500\ \mu\mathrm{m}$ diameter, unmyelinated): approximately $25\ \mathrm{m\ s^{-1}}$

Multiple sclerosis (MS): autoimmune destruction of the myelin sheath in the CNS, slowing or blocking nerve impulse conduction. Symptoms depend on which nerves are affected.

33. Synaptic Plasticity and the Brain

33.1 Long-Term Potentiation (LTP) in Detail

LTP is the cellular basis of learning and memory in the hippocampus:

1. A presynaptic neuron is stimulated repeatedly (high-frequency stimulation, e.g., 100 Hz for 1 second).
2. This causes a large, sustained depolarisation of the postsynaptic neuron (EPSPs summate).
3. The depolarisation is sufficient to activate NMDA receptors, allowing $\mathrm{Ca^{2+}}$ to enter the postsynaptic neuron.
4. \mathrm{Ca^{2+} activates $\mathrm{Ca^{2+}}$/calmodulin-dependent protein kinase II (CaMKII).
5. CaMKII phosphorylates AMPA receptors, causing them to be inserted into the postsynaptic membrane (more AMPA receptors $\to$ larger EPSPs to the same stimulus).
6. The synapse is now "strengthened": the same presynaptic stimulus produces a larger postsynaptic response.

33.2 Long-Term Depression (LTD)

LTD is the opposite of LTP: the weakening of a synapse following low-frequency stimulation. It involves removal of AMPA receptors from the postsynaptic membrane. LTD is important for:

• Forgetting irrelevant information.
• Clearing old memories to make room for new ones.
• Refining motor skills (removing unnecessary connections).

33.3 Neural Networks and the Brain

The brain contains approximately 86 billion neurons, each forming approximately 7,000 synapses, giving a total of approximately $6 \times 10^{14}$ synapses. The pattern of connections between neurons (the "connectome") underlies all brain function:

Brain Region	Approximate Number of Neurons	Function
Cerebral cortex	16 billion	Conscious thought, perception, language, memory, decision-making
Cerebellum	69 billion	Coordination, motor learning, balance
Brainstem	1 billion	Vital functions (breathing, heart rate, sleep-wake cycle)
Hippocampus	0.4 billion	Formation of new long-term memories (consolidation)
Amygdala	0.013 billion	Emotional processing (fear, aggression); emotional memories

33.4 Neurotransmitter Summary

Neurotransmitter	Type	Synthesised From	Primary Functions
Acetylcholine (ACh)	Biogenic amine	Choline + acetyl-CoA (via choline acetyltransferase)	NMJ (skeletal muscle contraction); parasympathetic nervous system; memory (hippocampus); Alzheimer's disease involves ACh neuron degeneration
Dopamine	Catecholamine	Tyrosine $\to$ L-DOPA $\to$ dopamine (via tyrosine hydroxylase and DOPA decarboxylase)	Reward pathway; motivation; voluntary movement; Parkinson's disease (dopamine deficiency); schizophrenia (excess dopamine in certain brain regions)
Noradrenaline (norepinephrine)	Catecholamine	Tyrosine $\to$ dopamine $\to$ noradrenaline (via dopamine $\beta$-hydroxylase)	Sympathetic nervous system (fight or flight); attention; arousal
Serotonin (5-HT)	Indolamine	Tryptophan $\to$ 5-HTP $\to$ serotonin (via tryptophan hydroxylase)	Mood regulation; sleep (converted to melatonin); appetite; depression (SSRIs increase serotonin availability)
GABA	Amino acid	Glutamate (via glutamate decarboxylase)	Main inhibitory neurotransmitter in the brain; reduces neuronal excitability; anxiety (GABA-A receptor target of benzodiazepines)
Glutamate	Amino acid	Glutamine $\to$ glutamate (via glutaminase)	Main excitatory neurotransmitter; learning and memory; excitotoxicity (excess glutamate damages neurons; implicated in stroke and ALS)
Glycine	Amino acid	Serine (via serine hydroxymethyltransferase)	Inhibitory neurotransmitter in the spinal cord and brainstem; motor control
Histamine	Biogenic amine	Histidine (via histidine decarboxylase)	Inflammatory response; arousal and wakefulness; gastric acid secretion
Endorphins	Peptide	Pro-opiomelanocortin (POMC) precursor	Pain relief (natural opioids); reward; euphoria; exercise-induced "runner's high"

34. The Autonomic Nervous System in Detail

34.1 Comparison of Sympathetic and Parasympathetic Systems

Feature	Sympathetic (Fight or Flight)	Parasympathetic (Rest and Digest)
Origin	Thoracic and lumbar regions of spinal cord (T1--L2)	Brainstem and sacral region of spinal cord (S2--S4)
Pre-ganglionic neurotransmitter	Acetylcholine (nicotinic receptors)	Acetylcholine (nicotinic receptors)
Post-ganglionic neurotransmitter	Noradrenaline (adrenergic receptors: $\alpha$ and $\beta$)	Acetylcholine (muscarinic receptors)
Pre-ganglionic fibre length	Short	Long
Post-ganglionic fibre length	Long	Short
General effect	Mobilises body for action: dilates pupils, increases heart rate, dilates bronchioles, inhibits digestion, stimulates glycogenolysis, dilates blood vessels to skeletal muscle	Conserves energy: constricts pupils, decreases heart rate, constricts bronchioles, stimulates digestion, promotes salivation
Adrenal medulla	Releases adrenaline and noradrenaline into blood (systemic effect)	Not involved

34.2 Key Examples

Organ	Sympathetic Effect	Parasympathetic Effect
Heart	Increases heart rate (SA node) and force of contraction	Decreases heart rate; slows AV node conduction
Lungs	Dilates bronchioles (relaxes smooth muscle via $\beta_2$ receptors)	Constricts bronchioles
Pupils	Dilates (radial muscles contract)	Constricts (circular muscles contract)
Digestive system	Inhibits peristalsis; reduces secretions; contracts sphincters	Stimulates peristalsis; increases secretions; relaxes sphincters
Bladder	Relaxes detrusor muscle; contracts internal sphincter (retention)	Contracts detrusor muscle; relaxes internal sphincter (micturition)
Blood vessels	Vasoconstriction (via $\alpha_1$ receptors, except skeletal muscle where $\beta_2$ causes vasodilation)	Minimal effect (few parasympathetic fibres to blood vessels)

35. Visual Processing in the Retina

35.1 Retinal Cell Types

Cell Type	Location	Function
Rod cell	Distributed throughout retina (except fovea)	Low-light vision; scotopic vision; 120 million per eye; one type of rhodopsin pigment; high sensitivity but low acuity; cannot distinguish colour
Cone cell	Concentrated in the fovea (central retina)	High-acuity colour vision; photopic vision; 6 million per eye; three types (L/red, M/green, S/blue); require bright light; lower sensitivity
Bipolar cell	Between photoreceptors and ganglion cells	Transmit signals from photoreceptors to ganglion cells; one type is ON-bipolar (depolarised by light), another is OFF-bipolar (hyperpolarised by light)
Ganglion cell	Innermost retinal layer	Axons form the optic nerve; transmit action potentials to the brain; some are directionally sensitive (detect motion)
Horizontal cell	Lateral connections between photoreceptors	Lateral inhibition; enhance contrast and edge detection
Amacrine cell	Lateral connections between bipolar and ganglion cells	Motion detection; temporal processing

35.2 Visual Acuity

Feature	Fovea	Peripheral Retina
Photoreceptor density	Very high (only cones)	Lower (mixture of rods and cones)
Convergence	1:1 (one cone to one bipolar to one ganglion)	Many rods converge onto one ganglion cell
Acuity	Very high (sharp, detailed vision)	Lower
Sensitivity	Low (requires bright light)	High (functions in dim light)
Colour vision	Yes (three cone types)	Limited (fewer cones)

35.3 The Blind Spot

The blind spot is where the optic nerve exits the retina. There are no photoreceptors at this point, so no light is detected.

• Normally not noticed because: (a) the other eye covers the blind spot; (b) the brain "fills in" the missing information using surrounding visual context.
• Can be demonstrated with a simple visual field test.

36. The Kidney: Nephron Function and Ultrafiltration

36.1 The Nephron

Region	Location	Function
Renal (Bowman's) capsule	Cortex	Site of ultrafiltration; encloses the glomerulus
Proximal convoluted tubule (PCT)	Cortex	Selective reabsorption: ALL glucose, ALL amino acids, ~85% Na$^+$, ~80% water, ALL vitamins; microvilli increase surface area; many mitochondria for active transport
Loop of Henle (descending limb)	Medulla	Water reabsorption (permeable to water, impermeable to salts); water moves out by osmosis into the hypertonic medulla
Loop of Henle (ascending limb)	Medulla	Active transport of Na$^+$ and Cl$^-$ out (Na$^+$/K$^+$ pump and Na$^+$/Cl$^-$ co-transporter); impermeable to water; creates the countercurrent multiplier
Distal convoluted tubule (DCT)	Cortex	Selective reabsorption and secretion; regulated by aldosterone (Na$^+$ reabsorption, K$^+$ secretion) and ADH (water reabsorption if needed)
Collecting duct	Medulla (passes through)	Final water reabsorption under ADH control; water moves out into hypertonic medulla

36.2 Ultrafiltration

Feature	Description
Site	Renal (Bowman's) capsule
Driving force	Hydrostatic pressure of blood in the glomerulus (~7 kPa); opposed by oncotic pressure of blood (~3.3 kPa) and hydrostatic pressure in the capsule (~2 kPa)
Net filtration pressure	~7 - 3.3 - 2 = ~1.7 kPa
Filtrate composition	Water, glucose, amino acids, urea, ions; NO large proteins, NO blood cells
Filter	Basement membrane (collagen and glycoproteins); podocyte foot processes (slits)
What is retained	Blood cells, platelets, and large plasma proteins (albumin, globulins)

37. Muscle Contraction: Sliding Filament Theory

37.1 Structure of a Sarcomere

Component	Location	Protein	Function
Thick filament	A band (centre of sarcomere)	Myosin	Has heads (cross-bridges) that bind to actin; ATPase activity
Thin filament	Extends from Z lines into A band; passes through I band	Actin (with tropomyosin and troponin)	Binding sites for myosin cross-bridges
Z line	Boundary of each sarcomere	$\alpha$-actinin	Anchors thin filaments
I band	Region around Z line; thin filaments only	--	Shortens during contraction
A band	Region containing thick filaments (and overlapping thin filaments)	--	Length stays constant during contraction
H zone	Central region of A band; thick filaments only (no thin filaments overlap)	--	Shortens during contraction; disappears at full contraction
M line	Centre of A band; holds thick filaments in place	--	Maintains filament alignment

37.2 The Cross-Bridge Cycle

Step	What Happens
1. Calcium release	Action potential arrives at neuromuscular junction $\to$ acetylcholine released $\to$ action potential in muscle fibre $\to$ sarcoplasmic reticulum releases $\mathrm{Ca^{2+}}$ ions into sarcoplasm
2. Calcium binds troponin	$\mathrm{Ca^{2+}}$ binds to troponin $\to$ troponin changes shape $\to$ tropomyosin moves away from actin binding sites
3. Cross-bridge formation	Myosin head (previously energised with ADP + Pi) binds to exposed actin binding site
4. Power stroke	Myosin head pivots, pulling the thin filament towards the centre of the sarcomere; ADP and Pi are released
5. Cross-bridge detachment	ATP binds to myosin head $\to$ myosin detaches from actin
6. Re-cocking	ATP is hydrolysed to ADP + Pi; energy released re-cocks the myosin head (back to step 3)

38. Neurodegenerative Diseases

38.1 Alzheimer's Disease

Feature	Description
Cause	Progressive degeneration of neurons in the cerebral cortex and hippocampus
Pathology	Amyloid plaques (extracellular deposits of $\beta$-amyloid protein); neurofibrillary tangles (intracellular deposits of hyperphosphorylated tau protein)
Symptoms	Progressive memory loss; confusion; disorientation; language problems; personality changes; eventually unable to care for self
Risk factors	Age (most common over 65); APOE4 gene (genetic risk factor); female sex; cardiovascular disease
Treatment	No cure; cholinesterase inhibitors (donepezil) temporarily improve symptoms by increasing acetylcholine availability

38.2 Parkinson's Disease

Feature	Description
Cause	Degeneration of dopamine-producing neurons in the substantia nigra (midbrain)
Pathology	Loss of dopaminergic neurons; Lewy bodies (intracellular inclusions of $\alpha$-synuclein protein)
Symptoms	Resting tremor (pill-rolling tremor); bradykinesia (slowness of movement); rigidity (stiffness); postural instability; reduced facial expression
Treatment	L-DOPA (levodopa; precursor to dopamine; crosses the blood-brain barrier); dopamine agonists; deep brain stimulation

38.3 Motor Neurone Disease (MND / ALS)

Feature	Description
Cause	Progressive degeneration of upper and lower motor neurones
Symptoms	Progressive muscle weakness and wasting; difficulty speaking, swallowing, and breathing; eventually fatal (usually within 2--5 years of diagnosis)
Pathology	TDP-43 protein aggregation in motor neurones
Treatment	No cure; riluzole (slows progression slightly); supportive care (ventilation, feeding tube)

39. Synaptic Transmission in Detail

39.1 Steps in Synaptic Transmission

Step	What Happens
1	Action potential arrives at the presynaptic terminal
2	Voltage-gated calcium ($\mathrm{Ca^{2+}}$) channels open; $\mathrm{Ca^{2+}}$ ions flow into the presynaptic terminal
3	$\mathrm{Ca^{2+}}$ triggers exocytosis of synaptic vesicles (vesicles fuse with the presynaptic membrane)
4	Neurotransmitter is released into the synaptic cleft
5	Neurotransmitter diffuses across the synaptic cleft (very fast; distance ~20--40 nm)
6	Neurotransmitter binds to specific receptors on the postsynaptic membrane
7	Ion channels on the postsynaptic membrane open (or close), causing a change in membrane potential
8	If the postsynaptic potential reaches threshold, an action potential is initiated in the postsynaptic neurone
9	Neurotransmitter is removed from the synaptic cleft (by reuptake into the presynaptic terminal, enzymatic breakdown, or diffusion)

39.2 Excitatory vs Inhibitory Synapses

Feature	Excitatory Synapse	Inhibitory Synapse
Neurotransmitter example	Acetylcholine (at neuromuscular junction), glutamate	GABA (in the brain), glycine (in the spinal cord)
Ion channels opened	$\mathrm{Na^+}$ channels (cations enter)	$\mathrm{Cl^-}$ channels (anions enter) or $\mathrm{K^+}$ channels ($\mathrm{K^+}$ exits)
Effect on postsynaptic membrane	Depolarisation (EPSP: excitatory postsynaptic potential)	Hyperpolarisation (IPSP: inhibitory postsynaptic potential)
Effect on likelihood of action potential	Increases (brings membrane potential closer to threshold)	Decreases (moves membrane potential further from threshold)

39.3 Synaptic Summation

Type	Description
Spatial summation	Multiple presynaptic neurones fire simultaneously; their EPSPs add together at the postsynaptic neurone to reach threshold
Temporal summation	A single presynaptic neurone fires rapidly in succession; EPSPs add together before the first one decays

40. The Reflex Arc

40.1 Components of a Reflex Arc

Component	Type of Neurone	Description
Receptor	--	Detects the stimulus (e.g., pain receptors in skin)
Sensory neurone	Afferent	Transmits impulses from the receptor to the CNS (spinal cord); cell body in the dorsal root ganglion
Relay neurone	Interneurone	Connects sensory neurone to motor neurone within the CNS
Motor neurone	Efferent	Transmits impulses from the CNS to the effector
Effector	--	Carries out the response (muscle contracts; gland secretes)

40.2 Features of Reflexes

Feature	Description
Involuntary	Does not require conscious thought; automatic
Fast	Short pathway (few synapses); rapid response
Protective	Protects the body from harm (e.g., withdrawal reflex from hot objects; blinking reflex)
Not learned	Innate (present from birth); does not require prior experience

40.3 Example: Withdrawal Reflex

1. Finger touches a hot object $\to$ pain receptors in the skin are stimulated.
2. Sensory neurone transmits impulse to the spinal cord.
3. Relay neurone passes the impulse to a motor neurone.
4. Motor neurone stimulates the biceps muscle (flexor) to contract $\to$ the arm is pulled away.
5. Simultaneously, a relay neurone inhibits the triceps (extensor) via an inhibitory interneurone $\to$ reciprocal inhibition prevents opposing muscles from working against each other.
6. The brain is informed (by a branch of the sensory neurone) so the person becomes consciously aware of the pain, but the reflex action has already occurred.

41. The Endocrine System: Key Hormones

41.1 Hypothalamus and Pituitary

Hormone	Source	Target	Effect
TRH (thyrotropin-releasing hormone)	Hypothalamus	Anterior pituitary	Stimulates release of TSH
CRH (corticotropin-releasing hormone)	Hypothalamus	Anterior pituitary	Stimulates release of ACTH
GnRH (gonadotropin-releasing hormone)	Hypothalamus	Anterior pituitary	Stimulates release of FSH and LH
ADH (vasopressin)	Hypothalamus (released by posterior pituitary)	Kidney collecting ducts	Increases water reabsorption
Oxytocin	Hypothalamus (released by posterior pituitary)	Uterus; mammary glands	Stimulates uterine contractions during labour; milk ejection during breastfeeding
TSH (thyroid-stimulating hormone)	Anterior pituitary	Thyroid gland	Stimulates thyroid hormone secretion
ACTH (adrenocorticotropic hormone)	Anterior pituitary	Adrenal cortex	Stimulates cortisol secretion
FSH	Anterior pituitary	Ovaries (follicles) / Testes (seminiferous tubules)	Stimulates follicle development / sperm production
LH	Anterior pituitary	Ovaries / Testes	Triggers ovulation / stimulates testosterone production
Prolactin	Anterior pituitary	Mammary glands	Stimulates milk production
Growth hormone (GH)	Anterior pituitary	Most tissues (liver, bones, muscles)	Stimulates growth; stimulates the liver to produce IGF-1

41.2 Thyroid and Adrenal Glands

Hormone	Source	Effect
Thyroxine ($\mathrm{T_4}$)	Thyroid gland	Stimulates basal metabolic rate; essential for growth and development; increases oxygen consumption and heat production
Cortisol	Adrenal cortex	Increases blood glucose (stimulates gluconeogenesis and glycogenolysis); suppresses the immune system; anti-inflammatory
Adrenaline	Adrenal medulla	Fight or flight response: increases heart rate, dilates bronchioles, dilates pupils, stimulates glycogenolysis
Aldosterone	Adrenal cortex	Increases $\mathrm{Na^+}$ reabsorption and $\mathrm{K^+}$ secretion in the kidney; increases blood volume and pressure

42. Sensory Receptors

42.1 How Sensory Receptors Work

Step	What Happens
1	Stimulus (e.g., light, pressure, temperature, chemicals) activates the receptor
2	The receptor acts as a transducer (converts one form of energy to another: stimulus energy $\to$ electrical energy in the form of a generator potential)
3	If the generator potential reaches threshold, it triggers an action potential in the sensory neurone
4	The action potential is transmitted to the CNS

42.2 Types of Sensory Receptors

Receptor Type	Stimulus Detected	Location	Mechanism
Pacinian corpuscle	Mechanical pressure / vibration	Deep in the skin, joints, tendons	Pressure deforms the corpuscle; stretches the sensory neurone membrane; opens stretch-mediated sodium channels; $\mathrm{Na^+}$ enters; depolarisation (generator potential)
Photoreceptor (rod/cone)	Light	Retina of the eye	Light is absorbed by visual pigment (rhodopsin in rods; photopsin in cones); pigment splits; triggers a cascade that closes $\mathrm{Na^+}$ channels; hyperpolarisation (generator potential)
Olfactory receptor	Chemical (volatile odorants)	Nasal epithelium	Odorant binds to G-protein coupled receptor on cilia; activates adenylate cyclase $\to$ cAMP $\to$ opens $\mathrm{Na^+}$ channels; depolarisation
Gustatory receptor	Chemical (dissolved tastants)	Taste buds on tongue	Tastant binds to receptor; depolarisation; action potential sent to brain
Baroreceptor	Blood pressure	Aortic arch, carotid sinus	Stretch of arterial wall by high blood pressure opens stretch-mediated channels; depolarisation; sends signals to the medulla (triggers vasodilation and reduced heart rate via the vagus nerve)

43. The Human Eye

43.1 Structure and Function

Component	Description	Function
Sclera	Tough, white, outer layer of the eye	Protection; maintains shape of the eyeball
Cornea	Transparent front part of the sclera	Refracts (bends) light as it enters the eye; provides most of the eye's focusing power
Conjunctiva	Thin, transparent membrane covering the sclera and inner eyelids	Protection; lubrication
Iris	Coloured ring of muscle that controls the size of the pupil	Controls the amount of light entering the eye (pupil dilation/constriction)
Pupil	Hole in the centre of the iris	Allows light to pass through to the lens and retina
Lens	Transparent, flexible, biconvex structure behind the iris	Fine focusing (accommodation); changes shape to focus on near or distant objects
Ciliary body	Ring of muscle and suspensory ligaments attached to the lens	Controls lens shape for accommodation
Retina	Light-sensitive layer at the back of the eye	Contains photoreceptors (rods and cones); converts light to electrical signals
Fovea	Small depression in the retina (highest cone density)	Area of sharpest vision (highest visual acuity)
Optic nerve	Bundle of ganglion cell axons exiting the eye	Transmits action potentials to the brain
Blind spot	Where the optic nerve exits the retina	No photoreceptors; no vision at this point

43.2 Accommodation

Distance	Ciliary Muscles	Suspensory Ligaments	Lens Shape	Focused On
Distant object	Relaxed	Taut	Thin (flattened)	Retina
Near object	Contracted	Slack	Thick (more curved)	Retina

44. Action Potentials in Detail

44.1 Stages of an Action Potential

Stage	What Happens	Membrane Potential
Resting potential	$\mathrm{Na^+}$/$\mathrm{K^+}$ pump maintains concentration gradients; membrane is more permeable to $\mathrm{K^+}$ than $\mathrm{Na^+}$ (leak channels); inside is negative relative to outside	-70 mV
Depolarisation	Stimulus causes voltage-gated $\mathrm{Na^+}$ channels to open; $\mathrm{Na^+}$ rushes in (down its electrochemical gradient); membrane potential becomes more positive	-70 mV $\to$ +40 mV
Repolarisation	Voltage-gated $\mathrm{Na^+}$ channels close; voltage-gated $\mathrm{K^+}$ channels open (with a delay); $\mathrm{K^+}$ rushes out (down its electrochemical gradient); membrane potential returns to negative	+40 mV $\to$ -70 mV
Hyperpolarisation	Voltage-gated $\mathrm{K^+}$ channels close slowly; membrane potential briefly becomes more negative than the resting potential	-70 mV $\to$ -80 mV (briefly)
Return to resting	$\mathrm{Na^+}$/$\mathrm{K^+}$ pump restores the original ion concentrations	-70 mV

44.2 Refractory Periods

Period	What Happens	Why It Matters
Absolute refractory period	Voltage-gated $\mathrm{Na^+}$ channels are inactivated; no new action potential can be generated regardless of stimulus strength	Ensures action potentials travel in one direction only (unidirectional propagation)
Relative refractory period	Some $\mathrm{Na^+}$ channels have recovered but $\mathrm{K^+}$ channels are still open; a stronger-than-normal stimulus can generate an action potential	Limits the maximum frequency of action potentials

45. Myelination and Saltatory Conduction

45.1 Myelin Sheath

Feature	Description
Structure	Multiple layers of cell membrane (from Schwann cells in the PNS; oligodendrocytes in the CNS) wrapped around the axon
Function	Insulates the axon; prevents ion leakage; increases the speed of action potential propagation
Nodes of Ranvier	Gaps in the myelin sheath (~1--3 mm apart); exposed axon membrane; voltage-gated $\mathrm{Na^+}$ channels are concentrated here

45.2 Saltatory Conduction

Feature	Description
Mechanism	Action potential "jumps" from one node of Ranvier to the next (does not propagate continuously along the axon)
Speed	Much faster than continuous conduction (up to 120 m/s in myelinated neurones vs ~0.5 m/s in unmyelinated neurones)
Why faster	The depolarisation at one node is sufficient to depolarise the next node to threshold (current flows under the myelin sheath and builds up at the next node)
Energy efficient	Fewer $\mathrm{Na^+}$/$\mathrm{K^+}$ pumps needed to restore ion gradients (only the nodes of Ranvier need repolarisation, not the entire axon membrane)

46. Diseases of the Nervous System

46.1 Multiple Sclerosis (MS)

Feature	Description
Cause	Autoimmune destruction of the myelin sheath in the CNS (brain and spinal cord)
Pathology	Inflammatory demyelination; scleroses (scar tissue) form where myelin has been destroyed
Symptoms	Vision problems (optic neuritis); muscle weakness, numbness, tingling; fatigue; cognitive changes; problems with coordination and balance
Progression	Relapsing-remitting (most common form): episodes of worsening (relapses) followed by periods of recovery (remissions)
Treatment	No cure; disease-modifying therapies (e.g., interferon-$\beta$, natalizumab, fingolimod) reduce relapse rate; corticosteroids for acute relapses; physiotherapy

46.2 Parkinson's Disease

Feature	Description
Cause	Progressive loss of dopamine-producing neurones in the substantia nigra
Pathology	Lewy bodies (intracellular inclusions of $\alpha$-synuclein protein) in surviving neurones
Motor symptoms	Resting tremor (pill-rolling); bradykinesia (slowness of movement); rigidity; postural instability; shuffling gait; reduced facial expression (mask-like face)
Non-motor symptoms	Depression; sleep disorders; constipation; loss of sense of smell (anosmia); cognitive decline (in advanced stages)
Treatment	L-DOPA (levodopa); dopamine agonists; MAO-B inhibitors; deep brain stimulation (DBS) for severe, drug-resistant cases

47. The Eye and Photoreception

47.1 Structure of the Human Eye

Structure	Function
Cornea	Transparent outer layer; provides most of the eye's focusing power (refraction); fixed curvature
Iris	Coloured ring of muscle; controls the size of the pupil (regulates light entry)
Pupil	Hole in the iris; diameter changes to control light intensity reaching the retina
Lens	Transparent, flexible structure behind the iris; changes shape (accommodation) to focus on near or distant objects
Ciliary body	Contains ciliary muscles and suspensory ligaments; controls lens shape
Retina	Light-sensitive layer at the back of the eye; contains photoreceptors (rods and cones)
Fovea	Area of the retina with the highest density of cones; sharpest vision (highest visual acuity)
Optic nerve	Carries impulses from the retina to the visual cortex in the brain
Blind spot	Where the optic nerve exits the eye; no photoreceptors; cannot detect light

47.2 Rods vs Cones

Feature	Rods	Cones
Distribution	Concentrated at the periphery of the retina	Concentrated at the fovea (centre of retina)
Sensitivity	Very sensitive to low light (scotopic vision)	Require bright light (photopic vision)
Colour vision	No (only one type of rhodopsin pigment)	Yes (three types: red, green, blue)
Visual acuity	Low (many rods share one ganglion cell; cannot distinguish fine detail)	High (each cone connects to its own ganglion cell)
Rhodopsin	Contains retinal + opsin; breaks down in bright light (bleaching)	Contains photopsin + retinal; three types with different absorption spectra

48. Drug Action on the Nervous System

48.1 How Drugs Affect Synaptic Transmission

Mechanism	Description	Example
Stimulates neurotransmitter release	Drug causes more vesicles to fuse with the presynaptic membrane	Black widow spider venom (causes massive ACh release)
Inhibits neurotransmitter release	Drug prevents vesicle fusion	Botulinum toxin (Botox); blocks ACh release at neuromuscular junctions; causes flaccid paralysis
Mimics neurotransmitter (agonist)	Drug binds to the postsynaptic receptor and activates it	Nicotine (nicotinic ACh receptor agonist); morphine (opioid receptor agonist)
Blocks neurotransmitter receptor (antagonist)	Drug binds to the postsynaptic receptor but does not activate it; prevents the real neurotransmitter from binding	Curare (nicotinic ACh receptor antagonist); blocks neuromuscular junction; causes paralysis
Inhibits enzyme that breaks down neurotransmitter	Drug prevents breakdown; neurotransmitter remains in the synaptic cleft for longer	Sarin nerve gas (inhibits acetylcholinesterase); organophosphate pesticides
Stimulates enzyme that breaks down neurotransmitter	Drug increases breakdown rate; reduces neurotransmitter effect	--

48.2 Effects of Specific Drugs

Drug	Type	Effect on Nervous System
Alcohol (ethanol)	Depressant	Increases the inhibitory effect of GABA; decreases excitatory effect of glutamate; overall: slows brain activity; reduces anxiety and inhibitions at low doses; causes loss of coordination, unconsciousness, and respiratory depression at high doses
Cocaine	Stimulant	Blocks reuptake of dopamine at synapses in the reward pathway; dopamine accumulates in the synaptic cleft; produces feelings of euphoria; highly addictive
Prozac (fluoxetine)	SSRI antidepressant	Selectively inhibits serotonin reuptake; serotonin remains in the synaptic cleft longer; increases serotonin signalling; takes 2--4 weeks for full therapeutic effect

49. Habituation and Learning

49.1 Habituation

Feature	Description
What it is	A simple form of learning in which an animal stops responding to a repeated, harmless stimulus
Example	Sea anemones retract their tentacles when touched; after repeated harmless touches, they no longer respond
Significance	Prevents the animal from wasting energy on responses to stimuli that are not important (e.g., background noise)
Characteristics	The response can recover if the stimulus is not presented for a while (spontaneous recovery); only the specific repeated stimulus is ignored (stimulus-specific)

49.2 Other Types of Learning

Type	Description	Example
Classical conditioning	An animal learns to associate a neutral stimulus with a meaningful stimulus	Pavlov's dogs: learned to associate a bell with food; salivated at the bell alone
Operant conditioning	An animal learns to associate a behaviour with a reward or punishment	Rats learn to press a lever to receive food (Skinner box)
Insight learning	An animal suddenly solves a problem without trial and error; requires reasoning	Chimpanzees stacking boxes to reach a banana; Sultan the chimp using a stick to reach fruit

50. Synaptic Transmission in Detail

50.1 Steps at a Cholinergic Synapse

Step	Description
1. Arrival of impulse	Action potential arrives at the presynaptic terminal (axon terminal)
2. Calcium influx	Voltage-gated calcium ion channels open; $\mathrm{Ca^{2+}}$ ions diffuse into the presynaptic terminal down their concentration gradient
3. Vesicle fusion	The influx of $\mathrm{Ca^{2+}}$ causes synaptic vesicles (containing the neurotransmitter acetylcholine, ACh) to move to and fuse with the presynaptic membrane
4. Exocytosis	ACh is released into the synaptic cleft by exocytosis
5. Diffusion	ACh diffuses across the synaptic cleft (very short distance; transmission is fast)
6. Receptor binding	ACh binds to specific receptor proteins (nicotinic ACh receptors) on the postsynaptic membrane; this causes sodium ion channels to open
7. Postsynaptic depolarisation	$\mathrm{Na^+}$ ions diffuse into the postsynaptic neurone; this causes depolarisation (excitatory postsynaptic potential, EPSP); if the EPSP reaches threshold, an action potential is triggered
8. Enzymatic breakdown	Acetylcholinesterase (in the synaptic cleft) hydrolyses ACh into choline and ethanoic acid (acetate); this prevents continuous stimulation of the postsynaptic neurone
9. Reuptake/recycling	Choline is taken back up into the presynaptic neurone by active transport; combined with acetyl-CoA to resynthesise ACh; stored in new vesicles

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tip

Diagnostic Test

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