Nervous System

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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.

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)

## 2. 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 $\mathrm{Na^+}$.

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

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

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

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

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

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

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.

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.

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 ($0.5$—$2\ \mathrm{m\ s^{-1}}$).

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

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

This is consistent with a myelinated axon of moderate diameter.

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.

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.

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

A single EPSP is 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.

## 5. Neurotransmitters

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.

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

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).

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).

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.

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.

## 7. Sensory Receptors

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.

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

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.

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 $5$—$10\ \mathrm{nm}$.

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.

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.

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)

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.

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.

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”

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.

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.

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.

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.

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

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

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

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

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) 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

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.

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.

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 ($\lambda$):

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

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.

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: $10$—$30\ \mathrm{ms}$.

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.

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.

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).

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.

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.

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.

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.

1. Confusing the resting potential with the action potential. The resting potential is a stable state maintained by the Na⁺/K⁺ pump and K⁺ leak channels (approximately −70 mV). The action potential is a transient event — a rapid depolarisation to +40 mV followed by repolarisation. The resting potential is maintained continuously; the action potential is an all-or-nothing event.

2. Stating that neurotransmitters “cross the synaptic cleft by diffusion” without mentioning receptors. The neurotransmitter diffuses across the cleft and binds to specific receptor proteins on the postsynaptic membrane. This binding opens ion channels, which causes the change in membrane potential. The specificity of neurotransmitter-receptor binding determines whether the synapse is excitatory or inhibitory.

3. Claiming 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).

4. Confusing spatial and temporal summation. Spatial summation: multiple presynaptic neurones fire simultaneously onto the same postsynaptic neurone. Temporal summation: a single presynaptic neurone fires rapidly in succession. Both combine EPSPs to reach threshold, but the mechanisms are different.

5. Thinking myelin speeds up the action potential by “insulating” it. 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.

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)

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.

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.

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.

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

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)

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.

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).

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

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

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.

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).

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).

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	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

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.

## 25. Reflex Arcs: Detailed Mechanisms

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).

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).

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.

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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$$ $$

• Biology
• Cells
• Genetics and DNA

The nervous system is the body’s communication network, and its speed comes from a beautifully simple trick: electricity. A neurone is essentially a long wire that can switch between two states --- resting (negative inside) and active (positive inside). When a stimulus is strong enough to reach the threshold, sodium channels snap open and positive charge rushes in, creating an electrical impulse that races down the axon. This is an all-or-nothing event: it either happens fully or not at all, just like a bullet leaving a gun --- the trigger either fires or it does not, and once fired, the bullet travels at full speed regardless of how hard you pulled.

At a synapse, the electrical signal is briefly converted into a chemical one --- neurotransmitter molecules cross the gap and bind to receptors on the next neurone, either exciting it or inhibiting it. This chemical step is what makes the nervous system flexible rather than just a hard-wired circuit: the same signal can be amplified, dampened, or redirected depending on which synapses are involved. Reflexes bypass the brain entirely --- the sensory neurone talks directly to a motor neurone via a relay neurone in the spinal cord, producing an immediate response before you have even consciously registered the danger.