Nervous System

Neuron Structure and Types

Structure of a Neuron

Neurons (nerve cells) are the fundamental functional units of the nervous system. They are specialised for transmitting electrical impulses (action potentials) from one part of the body to another.

Component	Structure	Function
Cell body (soma)	Contains the nucleus, cytoplasm, and organelles	Controls metabolic activity of the neuron; synthesises neurotransmitters
Dendrites	Short, branched extensions from the cell body	Receive impulses from other neurons or sensory receptors; transmit towards the cell body
Axon	Long, single fibre extending from the cell body	Carries impulses away from the cell body towards the axon terminal
Myelin sheath	Fatty insulating layer around the axon	Insulates the axon; speeds up impulse transmission by saltatory conduction
Nodes of Ranvier	Gaps in the myelin sheath at regular intervals (~1 mm apart)	Allow ions to flow in/out of the axon; action potential "jumps" between nodes (saltatory conduction)
Axon terminal	Branched endings of the axon	Release neurotransmitters into the synaptic cleft to stimulate the next neuron or effector
Schwann cells	Cells that form the myelin sheath (in the PNS)	Wrap around the axon, depositing layers of lipid (myelin) that insulate it

Types of Neurons

Type	Structure	Function	Location
Sensory (afferent)	Long axon; cell body in a side branch	Transmit impulses FROM receptors TO the CNS	Dorsal root ganglion; throughout the body
Relay (interneuron)	Short axon; many dendrites	Connect sensory and motor neurons; process information	Within the CNS (brain and spinal cord)
Motor (efferent)	Cell body in CNS; long axon to effector	Transmit impulses FROM the CNS TO effectors	Ventral horn of spinal cord; brainstem

Myelination

Myelin in the peripheral nervous system (PNS): Formed by Schwann cells. Each Schwann cell wraps around a short section of axon, creating a segment of myelin sheath. The gap between adjacent Schwann cells is a node of Ranvier.

Myelin in the central nervous system (CNS): Formed by oligodendrocytes. Each oligodendrocyte can myelinate multiple axon segments simultaneously (unlike Schwann cells, which myelinate only one segment).

Significance of myelination:

• Myelin acts as an electrical insulator, preventing current leakage across the axon membrane
• Forces depolarisation to occur only at the nodes of Ranvier
• The action potential "jumps" from node to node (saltatory conduction), which is much faster than continuous propagation along an unmyelinated axon
• Myelinated neurons conduct at speeds of approximately 100-120 m/s; unmyelinated neurons conduct at approximately 0.5-2 m/s

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Resting Potential

Establishment of the Resting Potential

When a neuron is not transmitting an impulse, it is said to be at its resting potential. The inside of the axon is negatively charged relative to the outside, typically at approximately -70 mV.

The resting potential is established and maintained by three factors:

1. The sodium-potassium pump ($\mathrm{Na}^+/\mathrm{K}^+$-ATPase):

• This active transport pump moves 3 $\mathrm{Na}^+$ ions OUT of the cell and 2 $\mathrm{K}^+$ ions INTO the cell for each ATP hydrolysed
• This creates a concentration gradient: high $\mathrm{Na}^+$ outside, high $\mathrm{K}^+$ inside
• The pump makes the inside more negative because more positive charge is pumped out than in (net loss of one positive charge per cycle)
• The pump operates continuously and is responsible for the long-term maintenance of the resting potential

2. Potassium leak channels:

• The axon membrane is much more permeable to $\mathrm{K}^+$ than to $\mathrm{Na}^+$ at rest (approximately 50-100 times more permeable)
• $\mathrm{K}^+$ ions diffuse out of the cell down their concentration gradient through these leak channels
• As $\mathrm{K}^+$ leaves, it carries positive charge out of the cell, making the inside more negative
• This outward diffusion of $\mathrm{K}^+$ is the primary cause of the negative resting potential

3. Impermeability to sodium:

• The membrane is very poorly permeable to $\mathrm{Na}^+$ at rest (few $\mathrm{Na}^+$ channels are open)
• Although there is a strong concentration gradient driving $\mathrm{Na}^+$ inward, very little $\mathrm{Na}^+$ can cross the membrane at rest
• This means the inward movement of $\mathrm{Na}^+$ does not counteract the outward movement of $\mathrm{K}^+$

The resting potential is therefore an electrochemical gradient: a combination of the concentration gradients of $\mathrm{Na}^+$ and $\mathrm{K}^+$ (chemical gradient) and the electrical potential difference (electrical gradient).

Ion	Intracellular Concentration (mM)	Extracellular Concentration (mM)	Direction of Concentration Gradient
$\mathrm{Na}^+$	15	145	Inward
$\mathrm{K}^+$	140	5	Outward
$\mathrm{Cl}^-$	10	110	Inward

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Action Potential

Phases of the Action Potential

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

Phase	Membrane Potential	Ion Movements	Channel Status
Resting	-70 mV	$\mathrm{Na}^+/\mathrm{K}^+$ pump maintains gradients; $\mathrm{K}^+$ leaks out	Most voltage-gated channels closed
Depolarisation	-70 mV to +40 mV	$\mathrm{Na}^+$ rushes IN through voltage-gated $\mathrm{Na}^+$ channels (down electrochemical gradient)	Voltage-gated $\mathrm{Na}^+$ channels open
Repolarisation	+40 mV to -70 mV	$\mathrm{K}^+$ rushes OUT through voltage-gated $\mathrm{K}^+$ channels (down concentration gradient)	$\mathrm{Na}^+$ channels close; $\mathrm{K}^+$ channels open
Hyperpolarisation (overshoot)	-70 mV to -80 mV	$\mathrm{K}^+$ continues to diffuse out (voltage-gated $\mathrm{K}^+$ channels are slow to close)	$\mathrm{Na}^+$ channels closed; $\mathrm{K}^+$ channels still open
Return to resting	-80 mV to -70 mV	$\mathrm{Na}^+/\mathrm{K}^+$ pump restores ionic gradients; $\mathrm{K}^+$ channels close	All channels return to resting state

Threshold and the All-or-Nothing Principle

• The threshold potential is approximately -55 mV. If the membrane depolarises to this level, voltage-gated $\mathrm{Na}^+$ channels open fully, triggering an action potential.
• If the stimulus does not depolarise the membrane to threshold, no action potential is generated.
• Once threshold is reached, the action potential is always the same size and shape, regardless of stimulus strength. This is the all-or-nothing principle.
• A stronger stimulus does not produce a larger action potential. Instead, it produces a higher frequency of action potentials.

The Refractory Period

After an action potential, there is a brief period during which the neuron cannot generate another action potential.

1. Absolute refractory period:

• Lasts approximately 1-2 ms
• The $\mathrm{Na}^+$ channels are inactivated (closed and cannot be reopened regardless of stimulus strength)
• A second action potential is impossible under any circumstances
• This ensures that action potentials travel in one direction only (unidirectional propagation)

2. Relative refractory period:

• Lasts approximately 2-4 ms (overlaps with the end of the absolute refractory period)
• The $\mathrm{Na}^+$ channels are recovering from inactivation, and the $\mathrm{K}^+$ channels are still open (membrane hyperpolarised)
• A larger-than-normal stimulus CAN trigger another action potential
• The neuron is less excitable than normal

Functional significance of the refractory period:

• Ensures unidirectional propagation of action potentials (prevents backward spread)
• Limits the maximum frequency of action potential firing
• Prevents action potentials from overlapping and summing

Saltatory Conduction

In myelinated neurons, the action potential does not travel continuously along the axon. Instead, depolarisation only occurs at the nodes of Ranvier (where the axon membrane is exposed). The current generated at one node spreads through the extracellular fluid and the axoplasm to depolarise the next node, "jumping" over the myelinated internode.

Advantages of saltatory conduction:

• Much faster: the action potential effectively skips the myelinated sections, travelling only between nodes
• Energy efficient: fewer ions need to be actively pumped back across the membrane (only at the nodes), reducing the workload on the $\mathrm{Na}^+/\mathrm{K}^+$ pump
• The myelin sheath reduces membrane capacitance, allowing depolarisation to spread further

Worked Example: Action Potential Speed

A myelinated sensory neuron has nodes of Ranvier spaced 1.2 mm apart. The action potential takes $10 \mu\mathrm{s}$ to propagate between consecutive nodes. Calculate the conduction velocity.

Solution

Conduction velocity = $\frac{\text{distance}}{\text{time}} = \frac{1.2 \times 10^{-3} \mathrm{ m}}{10 \times 10^{-6} \mathrm{ s}} = 120 \mathrm{ m/s}$

This is within the typical range for myelinated sensory neurons (approximately 100-120 m/s). An unmyelinated neuron of the same diameter would conduct at approximately 0.5-2 m/s, demonstrating the enormous speed advantage of myelination.

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Synaptic Transmission

Structure of a Cholinergic Synapse

A synapse is the junction between two neurons (or between a neuron and an effector). The most commonly studied synapse uses acetylcholine as the neurotransmitter.

Structure	Description
Pre-synaptic membrane	The membrane of the axon terminal of the first (pre-synaptic) neuron
Synaptic vesicles	Vesicles in the pre-synaptic terminal that store neurotransmitter molecules
Synaptic cleft	The narrow gap (~20 nm) between the pre-synaptic and post-synaptic membranes
Post-synaptic membrane	The membrane of the dendrite or cell body of the second (post-synaptic) neuron, containing receptor proteins
Mitochondria	Provide ATP for the synthesis of neurotransmitter and for reuptake of breakdown products

Mechanism of Synaptic Transmission

1. Arrival of action potential: An action potential arrives at the pre-synaptic terminal, depolarising the membrane.

2. Calcium influx: Voltage-gated $\mathrm{Ca}^{2+}$ channels in the pre-synaptic membrane open in response to depolarisation. $\mathrm{Ca}^{2+}$ ions diffuse into the pre-synaptic terminal down their concentration gradient.

3. Vesicle fusion: The influx of $\mathrm{Ca}^{2+}$ causes synaptic vesicles to fuse with the pre-synaptic membrane (exocytosis), releasing neurotransmitter into the synaptic cleft.

4. Diffusion: Neurotransmitter molecules diffuse across the synaptic cleft (~20 nm, taking approximately 0.5 ms).

5. Receptor binding: Neurotransmitter molecules bind to specific receptor proteins on the post-synaptic membrane. This binding causes ion channels to open.

6. Post-synaptic potential: If acetylcholine (an excitatory neurotransmitter) binds to the receptors, $\mathrm{Na}^+$ channels open. $\mathrm{Na}^+$ diffuses into the post-synaptic neuron, causing a small depolarisation called an excitatory post-synaptic potential (EPSP).

7. Summation: A single EPSP is usually insufficient to reach threshold. Multiple EPSPs from different synapses (spatial summation) or in rapid succession from the same synapse (temporal summation) can combine to depolarise the post-synaptic membrane to threshold, triggering a new action potential.

8. Neurotransmitter removal: Acetylcholine is rapidly broken down by the enzyme acetylcholinesterase, which is attached to the post-synaptic membrane. The breakdown products (choline and acetate) are taken back up by the pre-synaptic neuron and used to resynthesise acetylcholine.

Excitatory and Inhibitory Synapses

Feature	Excitatory Synapse	Inhibitory Synapse
Neurotransmitter	Acetylcholine, noradrenaline, glutamate	GABA, glycine
Ion channels opened	$\mathrm{Na}^+$ channels (also some $\mathrm{Ca}^{2+}$)	$\mathrm{Cl}^-$ channels (also some $\mathrm{K}^+$ channels)
Effect on membrane	Depolarisation (EPSP -- towards threshold)	Hyperpolarisation (IPSP -- further from threshold)
Probability of AP	Increases	Decreases

Inhibitory post-synaptic potential (IPSP): When an inhibitory neurotransmitter (e.g., GABA) binds to receptors on the post-synaptic membrane, $\mathrm{Cl}^-$ channels open. $\mathrm{Cl}^-$ diffuses into the neuron (or $\mathrm{K}^+$ diffuses out), making the inside even more negative (hyperpolarisation, to approximately -75 to -80 mV). This moves the membrane potential further from threshold, making it LESS likely that an action potential will be generated.

Summation

The post-synaptic neuron integrates all incoming signals (both excitatory and inhibitory) to determine whether threshold is reached.

Temporal summation: Multiple EPSPs from the SAME pre-synaptic neuron arrive in rapid succession, adding together before the first one decays. Each subsequent impulse adds to the depolarisation.

Spatial summation: Multiple EPSPs from DIFFERENT pre-synaptic neurons arrive simultaneously, adding together at the post-synaptic membrane. This allows integration of signals from multiple sources.

Why Synaptic Transmission is Unidirectional

Synaptic transmission occurs in one direction only (pre-synaptic to post-synaptic) because:

• Only the pre-synaptic terminal contains synaptic vesicles and the machinery for neurotransmitter release
• Only the post-synaptic membrane has the specific receptor proteins for the neurotransmitter
• Voltage-gated $\mathrm{Ca}^{2+}$ channels are only present on the pre-synaptic side
• Neurotransmitter is released only in response to depolarisation of the pre-synaptic terminal, not the post-synaptic membrane

Synaptic Delay

Transmission across a synapse takes approximately 0.5-1.0 ms, which is much slower than transmission along an axon. This delay is due to the time required for neurotransmitter release, diffusion, receptor binding, and ion channel opening. Synaptic delay limits the speed of reflexes and neural processing.

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Reflex Arcs

Components of a Reflex Arc

A reflex arc is the neural pathway that controls an involuntary, rapid response to a stimulus. It does not require conscious thought.

Component	Description
Receptor	Detects the stimulus and generates nerve impulses
Sensory neuron	Transmits impulses from the receptor to the CNS (spinal cord or brainstem)
Relay neuron	Connects the sensory neuron to the motor neuron within the CNS
Motor neuron	Transmits impulses from the CNS to the effector
Effector	Muscle or gland that carries out the response

Types of Reflex

1. Spinal reflex: The relay neurones and motor neurones are in the spinal cord. The brain is not involved in the initial response. Examples: withdrawal reflex, stretch reflex.

2. Cranial reflex: The relay and motor neurones are in the brain (brainstem). Examples: pupillary reflex, blinking reflex.

The Withdrawal (Escape) Reflex

When a person touches a hot object, the following sequence occurs:

1. Receptor: Pain receptors (nociceptors) in the skin detect heat/pain and generate impulses
2. Sensory neuron: Impulses travel along sensory neurones to the spinal cord
3. Relay neuron: Impulses pass to a relay neuron in the spinal cord
4. Motor neuron: Impulses are transmitted to the motor neuron
5. Effector: The biceps muscle of the upper arm contracts (flexor), pulling the hand away

Simultaneous actions:

• The relay neuron also sends impulses UP the spinal cord to the brain, so the person becomes aware of the pain after the reflex has occurred
• An inhibitory interneuron simultaneously inhibits the motor neuron supplying the antagonistic muscle (triceps -- extensor), preventing it from contracting and opposing the withdrawal. This is called reciprocal inhibition

Advantages of Reflex Arcs

• Speed: Involuntary and rapid, protecting the body before conscious thought occurs
• Protection: Prevents tissue damage from harmful stimuli
• No conscious input: Does not require processing by the brain, saving time
• Innate: Present from birth, not learned

The Pupillary Light Reflex

When light intensity increases:

1. Receptors: Photoreceptors in the retina detect increased light
2. Sensory neurons: Optic nerve (cranial nerve II) transmits impulses to the brain
3. Relay neurons: Impulses pass to the Edinger-Westphal nucleus in the midbrain
4. Motor neurons: Oculomotor nerve (cranial nerve III) transmits impulses to the circular muscles of the iris
5. Effector: Circular muscles contract, constricting the pupil and reducing the amount of light entering the eye

This is a cranial reflex and a consensual reflex -- shining light in one eye causes both pupils to constrict because the relay neurons send impulses to both Edinger-Westphal nuclei.

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Sense Organs

The Eye: Detailed Structure

Component	Structure and Function
Sclera	Tough, white outer layer; protects the eye and maintains shape
Cornea	Transparent front part of the sclera; refracts light as it enters the eye
Conjunctiva	Thin transparent membrane covering the sclera and inner eyelids; produces mucus to lubricate the eye
Choroid	Pigmented, vascular layer; absorbs stray light to prevent reflection; supplies nutrients to the retina
Retina	Light-sensitive layer at the back of the eye; contains photoreceptors (rods and cones)
Fovea	Small depression at the centre of the retina; contains only cones; highest visual acuity (point of sharpest vision)
Blind spot (optic disc)	Point where the optic nerve exits the eye; no photoreceptors, so no vision at this point
Iris	Coloured ring of muscle; controls the size of the pupil (circular muscles constrict, radial muscles dilate)
Pupil	Hole in the centre of the iris; allows light to enter the eye
Lens	Transparent, elastic structure; changes shape to focus light on the retina (accommodation)
Ciliary body	Ring of muscle that controls the shape of the lens; also secretes aqueous humour
Suspensory ligaments	Connect the ciliary body to the lens; transmit tension from the ciliary muscles to the lens
Aqueous humour	Watery fluid between the cornea and lens; maintains pressure and provides nutrients
Vitreous humour	Jelly-like fluid filling the space behind the lens; maintains the shape of the eye and transmits light
Optic nerve	Transmits impulses from the retina to the brain

Adaptations of the Eye for Function

Adaptation	Function
Transparent cornea and lens	Allow light to pass through to the retina
Suspensory ligaments and ciliary muscles	Enable the lens to change shape for accommodation (focusing on near and distant objects)
Two types of photoreceptor	Rods for dim light and peripheral vision; cones for colour and detailed central vision
Fovea packed with cones	Highest visual acuity at the centre of the visual field
Iris controls pupil size	Regulates the amount of light entering the eye (protects retina from damage in bright light)
Aqueous and vitreous humours	Maintain the shape of the eyeball and keep the retina pressed against the choroid

Photoreceptors: Rods and Cones

Feature	Rods	Cones
Sensitivity	Very high; work in dim light (scotopic vision)	Lower; work in bright light (photopic vision)
Colour vision	Cannot distinguish colour (only one type of rhodopsin pigment)	Three types (red, green, blue iodopsin); enable colour vision
Visual acuity	Low resolution (many rods share one bipolar neuron)	High resolution (one cone per bipolar neuron in the fovea)
Distribution	Concentrated at the periphery of the retina (absent at the fovea)	Concentrated at the fovea (sparse at the periphery)
Pigment	Rhodopsin (bleached in bright light; takes time to regenerate)	Iodopsin (three types with different absorption spectra)
Role	Peripheral vision; detecting movement; night vision	Central vision; colour discrimination; fine detail

The Ear: Hearing and Balance

The ear has two functions: hearing and balance.

Hearing pathway:

1. Sound waves collected by the pinna and directed into the ear canal
2. Sound waves cause the eardrum (tympanic membrane) to vibrate
3. Vibrations amplified by the ossicles (malleus, incus, stapes) -- lever action and area ratio amplify force approximately 20 times
4. Stapes pushes against the oval window, creating pressure waves in the perilymph fluid of the cochlea
5. Pressure waves cause the basilar membrane to vibrate
6. Hair cells (stereocilia) on the basilar membrane bend against the tectorial membrane
7. Bending of hair cells generates nerve impulses in the auditory nerve
8. Impulses transmitted to the auditory cortex of the brain, where sound is interpreted

Frequency discrimination: Different frequencies of sound cause different parts of the basilar membrane to vibrate. High-frequency sounds cause vibration near the base (near the oval window); low-frequency sounds cause vibration near the apex. This is the place theory of hearing.

Balance (equilibrium):

• The semicircular canals (three orthogonal canals) detect rotational acceleration of the head. Each canal contains endolymph fluid and hair cells in a swelling called the ampulla. Movement of the head causes the fluid to lag behind, bending the hair cells and generating impulses sent to the cerebellum.
• The utricle and saccule detect linear acceleration and the position of the head relative to gravity. They contain otoliths (calcium carbonate crystals) that move in response to gravity, bending hair cells.

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The Central Nervous System

The Brain

The brain is the main coordinating centre of the nervous system. It receives sensory input, processes information, and sends motor output.

Region	Structure	Function
Cerebrum	Two cerebral hemispheres (left, right)	Higher-order functions: conscious thought, memory, learning, language, decision-making, reasoning, personality
Cerebral cortex	Outer layer of grey matter	Contains motor areas (control voluntary movement), sensory areas (receive sensory input), association areas (interpretation)
Corpus callosum	Bundle of nerve fibres	Connects the two cerebral hemispheres, allowing communication between them
Hypothalamus	Small region below the thalamus	Controls the pituitary gland; regulates body temperature, hunger, thirst, blood water potential; produces ADH and releasing hormones
Pituitary gland	Pea-sized gland below the hypothalamus	"Master gland" -- secretes hormones controlling other endocrine glands (FSH, LH, TSH, ACTH, GH); posterior lobe stores ADH and oxytocin
Thalamus	Above the hypothalamus	Relay station for sensory impulses (except olfaction) to the cerebral cortex; filters sensory information before it reaches conscious awareness
Medulla oblongata	Lowest part of the brainstem	Controls involuntary (autonomic) functions: breathing rate, heart rate, blood pressure, swallowing, coughing, sneezing
Cerebellum	Below the cerebrum, behind the brainstem	Coordinates movement and balance; fine-tunes motor activity; maintains posture; involved in motor learning
Pons	Above the medulla	Relays signals between the cerebrum and cerebellum; helps regulate breathing rhythm

The Spinal Cord

The spinal cord runs from the medulla oblongata down the vertebral column. It has two main functions:

1. Transmission of nerve impulses: Ascending tracts carry sensory information up to the brain; descending tracts carry motor commands from the brain to effectors.

2. Reflex centre: Contains relay neurons that form the central component of spinal reflex arcs (e.g., withdrawal reflex, stretch reflex).

Cross-sectional structure of the spinal cord:

Feature	Description
Grey matter	Central H-shaped region; contains cell bodies of relay neurons, motor neurons, and interneurons
White matter	Outer region; contains myelinated axons (sensory ascending tracts and motor descending tracts)
Central canal	Small channel running the length of the cord; contains cerebrospinal fluid (CSF)
Dorsal root	Contains sensory neuron axons entering the spinal cord
Ventral root	Contains motor neuron axons leaving the spinal cord
Dorsal root ganglion	Swelling containing cell bodies of sensory neurons

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The Autonomic Nervous System

Overview

The autonomic nervous system (ANS) controls involuntary body functions such as heart rate, digestion, breathing rate, and pupil size. It has two divisions that generally have antagonistic effects.

Feature	Sympathetic Nervous System	Parasympathetic Nervous System
General function	"Fight or flight" -- prepares body for action/stress	"Rest and digest" -- promotes calm, maintenance activities
Neurotransmitter (pre-ganglionic)	Acetylcholine	Acetylcholine
Neurotransmitter (post-ganglionic)	Noradrenaline (at most effectors)	Acetylcholine
Origin	Thoracic and lumbar regions of spinal cord	Brainstem and sacral region of spinal cord
Ganglia location	Close to the spinal cord (paravertebral chain)	Close to or within the target organ
Preganglionic fibre	Short	Long
Postganglionic fibre	Long	Short
Heart rate	Increases	Decreases
Pupil size	Dilates	Constricts
Bronchioles	Dilates (increases air intake)	Constricts
Digestive activity	Decreases (inhibits peristalsis; reduces secretions)	Increases (stimulates peristalsis and secretions)
Blood glucose	Increases (stimulates glycogenolysis)	Decreases
Blood vessels	Vasoconstriction in skin and gut; vasodilation in muscles	No significant effect on most blood vessels

Nervous Control of Heart Rate

The heart has its own intrinsic pacemaker -- the sinoatrial (SA) node -- which generates electrical impulses that cause the heart to beat at approximately 60-80 beats per minute at rest. However, the autonomic nervous system modifies this rate.

Sympathetic stimulation (increases heart rate):

1. During exercise, stress, or excitement, the sympathetic nervous system is activated
2. Noradrenaline is released at the SA node
3. Noradrenaline binds to beta-1 adrenergic receptors on the SA node cells
4. This increases the rate of depolarisation of the SA node cells, causing them to reach threshold faster
5. The SA node fires more frequently, increasing heart rate
6. Additionally, sympathetic stimulation increases the force of contraction (stroke volume), increasing cardiac output

Parasympathetic stimulation (decreases heart rate):

1. During rest, the parasympathetic nervous system dominates
2. The vagus nerve (cranial nerve X) releases acetylcholine at the SA node
3. Acetylcholine binds to muscarinic receptors on the SA node cells
4. This slows the rate of depolarisation of the SA node cells (hyperpolarises them slightly)
5. The SA node takes longer to reach threshold, decreasing heart rate

Adrenaline (from the adrenal medulla):

• Released into the blood during the "fight or flight" response
• Binds to beta-1 receptors on the heart, increasing heart rate and stroke volume
• Effects last longer than nervous stimulation because the hormone remains in the blood until broken down by the liver

Nervous Control of Breathing Rate

Breathing rate is controlled by the ventilation centre (respiratory centre) in the medulla oblongata.

Normal breathing cycle:

1. The ventilation centre sends rhythmic impulses to the intercostal muscles (between ribs) and diaphragm via the phrenic and intercostal nerves
2. These impulses cause the muscles to contract: the diaphragm flattens and the ribs move up and out
3. Lung volume increases, pressure decreases below atmospheric, and air rushes in (inhalation)
4. When the impulses stop, the muscles relax: the diaphragm curves up and ribs move down and in
5. Lung volume decreases, pressure increases above atmospheric, and air is forced out (exhalation)

Chemical control of breathing rate:

• $\mathrm{CO}_2$ concentration is the primary stimulus (not $\mathrm{O}_2$ concentration)
• Increased $\mathrm{CO}_2$ in the blood lowers blood pH (carbonic acid: $\mathrm{CO}_2 + \mathrm{H}_2\mathrm{O} \rightleftharpoons \mathrm{H}_2\mathrm{CO}_3 \rightleftharpoons \mathrm{H}^+ + \mathrm{HCO}_3^-$)
• Chemoreceptors in the aorta (aortic body) and carotid arteries (carotid body) detect increased $\mathrm{CO}_2$ / decreased pH
• Additional chemoreceptors in the medulla itself (central chemoreceptors) respond to $\mathrm{H}^+$ in the CSF
• These receptors send impulses to the ventilation centre, which increases the rate and depth of breathing
• $\mathrm{O}_2$ concentration is only monitored by chemoreceptors in the aortic and carotid bodies when it drops significantly (below approximately 60 mmHg)

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Sense Organs

The Eye

Structure of the eye:

Component	Description	Function
Sclera	Tough, white, fibrous outer layer of the eye	Protects the eye; provides attachment points for the extrinsic muscles that move the eye
Cornea	Transparent front part of the sclera; curved	Refracts (bends) light as it enters the eye; provides most of the eye's focusing power (~2/3 of the total refraction)
Conjunctiva	Thin, transparent membrane covering the sclera and inner eyelids	Protects and lubricates the eye surface
Iris	Coloured ring of muscle tissue behind the cornea	Controls the size of the pupil; regulates the amount of light entering the eye
Pupil	Hole in the centre of the iris	Allows light to pass through to the retina
Lens	Transparent, flexible, biconvex structure behind the iris and pupil	Fine-tunes focusing (accommodation); changes shape to focus on objects at different distances
Ciliary body	Ring of muscle tissue connected to the lens by suspensory ligaments	Controls the shape of the lens (accommodation)
Retina	Light-sensitive layer at the back of the eye; contains photoreceptor cells (rods and cones)	Converts light energy into electrical nerve impulses (transduction)
Fovea	Small depression in the retina at the centre of the macula; highest concentration of cones	Area of sharpest vision (highest visual acuity); colour vision is best here
Optic nerve	Bundle of nerve fibres carrying impulses from the retina to the brain	Transmits visual information to the visual cortex in the occipital lobe
Blind spot	Area where the optic nerve leaves the retina (optic disc)	No photoreceptors; cannot detect light; the brain fills in the missing information
Aqueous humour	Clear, watery fluid in the space between the cornea and the lens (anterior chamber)	Maintains the shape of the front of the eye; provides nutrients to the cornea and lens; refracts light slightly
Vitreous humour	Clear, jelly-like substance filling the space between the lens and the retina (posterior chamber)	Maintains the shape of the eyeball; keeps the retina pressed against the back of the eye
Choroid	Pigmented, vascular layer between the sclera and the retina	Provides oxygen and nutrients to the retina; contains pigment (melanin) that absorbs stray light and prevents internal reflection

Accommodation

Accommodation is the process by which the eye changes focus to see objects at different distances.

Distance	Ciliary Muscles	Suspensory Ligaments	Lens Shape	Focal Point
Distant object	Relaxed	Taut (pulled tight)	Thin, flattened	On the retina
Near object	Contracted	Slack (loose)	Thick, more curved	On the retina

Mechanism:

1. Light from a distant object is nearly parallel; the relaxed lens is thin enough to focus it on the retina
2. Light from a near object is diverging; the thin lens would focus it behind the retina (image would be blurry)
3. The ciliary muscles contract, reducing the diameter of the ciliary body
4. This causes the suspensory ligaments to go slack (they are no longer under tension)
5. The elastic lens recoils and becomes more rounded (thicker, more curved)
6. The thicker lens has greater refracting power and brings the diverging light rays to focus on the retina

Rods vs Cones

Feature	Rods	Cones
Number	~120 million per eye	~6 million per eye
Distribution	Distributed throughout the retina, concentrated at the periphery; absent from the fovea	Concentrated in the fovea (centre of the macula); very few at the periphery
Sensitivity to light	Very sensitive; function well in dim light (scotopic vision)	Less sensitive; require bright light (photopic vision)
Colour vision	No; only one type of rod pigment (rhodopsin)	Yes; three types of cones (S-cones for blue, M-cones for green, L-cones for red); enable trichromatic colour vision
Visual acuity (detail)	Low; many rods share a single ganglion cell connection, so the brain cannot distinguish which individual rod was stimulated	High; each cone has its own dedicated ganglion cell connection, so the brain can precisely locate the stimulus
Response speed	Slow to respond and recover (take longer to adapt to changes in light intensity)	Fast to respond and recover
Used for	Peripheral vision; night vision; detecting motion	Central vision; colour vision; fine detail (reading, recognising faces)

The Ear

Structure and function:

Component	Description	Function
Pinna (auricle)	Visible outer part of the ear; made of cartilage covered by skin	Collects sound waves and directs them into the ear canal
Ear canal (auditory meatus)	Tube leading from the pinna to the eardrum	Directs sound waves to the tympanum; contains wax-producing glands that protect the ear from dust and microorganisms
Tympanum (eardrum)	Thin, flexible membrane at the end of the ear canal	Vibrates when sound waves reach it; transfers vibrations to the ossicles
Ossicles	Three tiny bones: malleus (hammer), incus (anvil), stapes (stirrup); smallest bones in the body	Amplify the vibrations from the tympanum (by about 20x) and transmit them to the oval window of the cochlea
Oval window	Membrane-covered opening between the middle ear and the inner ear (cochlea)	Receives vibrations from the stapes; transmits them to the fluid in the cochlea
Cochlea	Coiled, fluid-filled tube in the inner ear; contains the organ of Corti (hair cells)	Converts vibrations into electrical nerve impulses; different parts of the cochlea respond to different frequencies
Round window	Membrane-covered opening below the oval window	Allows the fluid in the cochlea to move; dissipates the energy of the vibrations
Semi-circular canals	Three fluid-filled loops at right angles to each other in the inner ear	Detect rotational movement of the head (balance and equilibrium)
Auditory nerve	Carries impulses from the cochlea to the auditory cortex in the temporal lobe	Transmits sound information to the brain for interpretation
Eustachian tube	Tube connecting the middle ear to the nasopharynx (back of the throat)	Equalises air pressure on both sides of the tympanum; allows the eardrum to vibrate freely

Hearing mechanism:

1. Sound waves are collected by the pinna and directed into the ear canal
2. The sound waves cause the tympanum to vibrate
3. The ossicles amplify the vibrations and transmit them to the oval window
4. The oval window vibrates, creating pressure waves in the fluid (perilymph) inside the cochlea
5. The pressure waves cause the basilar membrane in the cochlea to vibrate; different frequencies cause different parts of the basilar membrane to vibrate most (the base vibrates to high frequencies; the apex vibrates to low frequencies)
6. Hair cells (stereocilia) on the organ of Corti bend as the basilar membrane vibrates
7. Bending of the stereocilia opens ion channels, creating a receptor potential
8. This triggers the release of neurotransmitter at the base of the hair cells, stimulating sensory neurons
9. Impulses travel along the auditory nerve to the auditory cortex in the temporal lobe, where the sound is interpreted

The Skin (Integumentary System)

Structure	Description	Function
Epidermis	Outer layer of skin; contains keratinocytes (produce keratin), melanocytes (produce melanin), and Langerhans cells (immune cells)	Barrier against pathogens, UV radiation, and water loss; melanin provides UV protection
Dermis	Inner layer of skin; contains blood vessels, nerves, hair follicles, sweat glands, sebaceous glands, sensory receptors	Provides structural support; nourishment; temperature regulation; sensation
Hypodermis (subcutaneous layer)	Layer of fat and connective tissue below the dermis	Insulation; energy storage; cushioning
Thermoreceptors	Nerve endings in the dermis that detect temperature changes	Detect heat and cold; relay information to the hypothalamus
Mechanoreceptors	Nerve endings in the dermis that detect pressure and touch	Detect pressure, vibration, and texture; relay information to the somatosensory cortex
Nociceptors	Nerve endings that detect pain (tissue damage)	Detect harmful stimuli; initiate protective reflexes
Sweat glands (eccrine)	Coiled tubular glands in the dermis that produce sweat	Thermoregulation: sweat evaporates from the skin surface, removing heat
Hair erector muscles	Small muscles attached to hair follicles	Contract in cold conditions (causing goosebumps), trapping a layer of insulating air next to the skin

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Drugs and the Nervous System

How Drugs Affect Synaptic Transmission

Many drugs exert their effects by interfering with synaptic transmission. Understanding these mechanisms is important for both the DSE specification and for understanding the basis of addiction and medicine.

Mechanism	Description	Example Drug	Effect
Agonist	Mimics the neurotransmitter by binding to and activating the receptor	Nicotine (acetylcholine receptor agonist)	Stimulates the postsynaptic neuron
Antagonist	Blocks the receptor, preventing the neurotransmitter from binding	Curare (acetylcholine receptor antagonist)	Prevents synaptic transmission; causes paralysis
Inhibits neurotransmitter breakdown	Blocks the enzyme that breaks down the neurotransmitter, prolonging its effect	Sarin (inhibits acetylcholinesterase)	Acetylcholine accumulates; overstimulation; muscle spasm
Stimulates neurotransmitter release	Causes more neurotransmitter to be released from the pre-synaptic terminal	Amphetamine (stimulates dopamine and noradrenaline release)	Increased stimulation of postsynaptic neurons
Inhibits neurotransmitter release	Prevents neurotransmitter release from the pre-synaptic terminal	Botulinum toxin (prevents acetylcholine release)	Flaccid paralysis; used medically for muscle spasms
Blocks reuptake	Prevents the pre-synaptic neuron from recycling the neurotransmitter, increasing its concentration in the cleft	Cocaine (blocks dopamine reuptake); SSRIs (block serotonin reuptake)	Prolonged effect of neurotransmitter; mood elevation
Blocks receptor on post-synaptic neuron	Binds to the receptor without activating it, preventing the real neurotransmitter from binding	Ketamine (NMDA receptor blocker)	Disrupts normal synaptic signalling

Effects of Drugs on the Body

Nicotine:

• Binds to nicotinic acetylcholine receptors in the brain, stimulating dopamine release in the reward pathway
• Causes initial stimulation (increased alertness, heart rate, blood pressure)
• Highly addictive because it activates the brain's reward system
• Long-term use is associated with cardiovascular disease, lung cancer (through smoking), and reduced lung function

Alcohol (ethanol):

• Crosses the blood-brain barrier and affects multiple neurotransmitter systems:
  • Enhances GABA activity (inhibitory neurotransmitter): slows brain function, reduces anxiety, impairs coordination
  • Inhibits glutamate (excitatory neurotransmitter): further depresses brain activity
  • Increases dopamine release in the reward pathway: contributes to addictive potential
• Short-term effects: impaired judgement, reduced coordination, slurred speech, slowed reaction time
• Long-term effects: liver damage (cirrhosis), brain damage, cardiovascular disease, addiction

Worked Example: Nervous Control During Exercise

During intense exercise, a person's breathing rate increases from 15 breaths/min to 40 breaths/min, and heart rate increases from 70 bpm to 180 bpm. Explain the nervous and hormonal mechanisms responsible for these changes.

Solution

Increased breathing rate:

• Increased muscle respiration produces more $\mathrm{CO}_2$ as a waste product
• Blood $\mathrm{CO}_2$ concentration rises, lowering blood pH
• Peripheral chemoreceptors (aortic body, carotid body) and central chemoreceptors (medulla) detect the increased $\mathrm{CO}_2$ / decreased pH
• These chemoreceptors send more impulses to the ventilation centre in the medulla
• The ventilation centre sends more frequent impulses to the intercostal muscles and diaphragm
• Breathing rate and depth increase, removing more $\mathrm{CO}_2$ from the blood

Increased heart rate:

• The sympathetic nervous system is activated during exercise
• Sympathetic nerve impulses release noradrenaline at the SA node, increasing the rate of pacemaker depolarisation
• The adrenal medulla releases adrenaline into the blood, which binds to beta-1 receptors on the heart, further increasing heart rate and stroke volume
• Proprioceptors in muscles and joints detect movement and send signals to the cardiovascular centre in the medulla, which relays impulses via the sympathetic nervous system to increase heart rate

Both responses are examples of negative feedback -- when $\mathrm{CO}_2$ levels return to normal, the chemoreceptors reduce their firing, and the ventilation centre decreases breathing rate accordingly.

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Common Pitfalls

1. Writing that the action potential "travels" along the neuron: The action potential does not physically move. Rather, it is a local reversal of membrane potential that is regenerated at each point along the axon. Each section of the membrane undergoes depolarisation in sequence, passing the signal along like a wave.

2. Confusing the direction of ion movement during the action potential: During depolarisation, $\mathrm{Na}^+$ moves INTO the cell (not out). During repolarisation, $\mathrm{K}^+$ moves OUT of the cell (not in). This is counterintuitive because the resting potential is negative, but remember: depolarisation makes the inside more positive (positive ions enter), and repolarisation restores the negative charge (positive ions leave).

3. Stating that the $\mathrm{Na}^+/\mathrm{K}^+$ pump is responsible for the action potential: The pump maintains the gradients but is too slow to directly cause the action potential. The rapid changes during the action potential are caused by voltage-gated ion channels (diffusion, not active transport). The pump restores the gradients AFTER the action potential.

4. Writing that a stronger stimulus produces a larger action potential: This violates the all-or-nothing principle. A stronger stimulus produces more action potentials per second (higher frequency), not larger ones. The amplitude of each action potential is constant.

5. Confusing the refractory period with fatigue: The refractory period is a normal, brief period after each action potential during which the neuron cannot fire again. It is not caused by fatigue or exhaustion. Fatigue refers to a decline in response over a sustained period of stimulation.

6. Writing that neurotransmitter is released from both sides of the synapse: Only the pre-synaptic terminal releases neurotransmitter. The post-synaptic membrane only has receptors. This is what makes transmission unidirectional.

7. Confusing spatial and temporal summation: Spatial summation involves multiple DIFFERENT pre-synaptic neurons firing simultaneously. Temporal summation involves the SAME pre-synaptic neuron firing rapidly in succession. Both can cause the post-synaptic membrane to reach threshold.

8. Writing that rods are responsible for colour vision: Rods are responsible for vision in dim light and cannot distinguish colour. Only cones provide colour vision (three types: red, green, blue). This is why colours appear washed out at night.

9. Confusing the sympathetic and parasympathetic nervous systems: Sympathetic = fight or flight (noradrenaline at most effectors; increases heart rate, dilates pupils, inhibits digestion). Parasympathetic = rest and digest (acetylcholine at all effectors; decreases heart rate, constricts pupils, stimulates digestion).

10. Writing that $\mathrm{O}_2$ concentration is the primary stimulus for breathing: Under normal conditions, $\mathrm{CO}_2$ concentration (and the resulting change in blood pH) is the primary stimulus for breathing rate. $\mathrm{O}_2$ concentration only becomes a significant stimulus when it drops dangerously low.

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Problem Set

Problem 1: Explain how the resting potential of approximately -70 mV is established and maintained in a neuron. In your answer, refer to the roles of the sodium-potassium pump, potassium leak channels, and membrane permeability.

If you get this wrong, revise: Resting Potential

Solution

The resting potential of approximately -70 mV is established by three factors:

1. The sodium-potassium pump ($\mathrm{Na}^+/\mathrm{K}^+$-ATPase) actively transports 3 $\mathrm{Na}^+$ ions out and 2 $\mathrm{K}^+$ ions in per ATP hydrolysed. This creates concentration gradients (high $\mathrm{Na}^+$ outside, high $\mathrm{K}^+$ inside) and a net outward movement of positive charge.

2. Potassium leak channels make the membrane much more permeable to $\mathrm{K}^+$ than to $\mathrm{Na}^+$ at rest. $\mathrm{K}^+$ diffuses out of the cell down its concentration gradient, carrying positive charge out and making the inside more negative.

3. Low $\mathrm{Na}^+$ permeability means that despite the strong inward concentration gradient for $\mathrm{Na}^+$, very little $\mathrm{Na}^+$ enters the cell at rest, so the outward $\mathrm{K}^+$ diffusion is not counteracted.

The resting potential is maintained because the $\mathrm{Na}^+/\mathrm{K}^+$ pump continuously compensates for the slow leakage of ions, restoring the concentration gradients over time.

Problem 2: Describe the sequence of events at a cholinergic synapse that leads to transmission of an impulse from one neuron to the next. Explain why transmission only occurs in one direction.

If you get this wrong, revise: Synaptic Transmission

Solution

1. An action potential arrives at the pre-synaptic terminal, depolarising the membrane.
2. Voltage-gated $\mathrm{Ca}^{2+}$ channels open; $\mathrm{Ca}^{2+}$ ions diffuse into the terminal.
3. $\mathrm{Ca}^{2+}$ causes synaptic vesicles to fuse with the pre-synaptic membrane, releasing acetylcholine into the synaptic cleft (exocytosis).
4. Acetylcholine diffuses across the synaptic cleft and binds to receptor proteins on the post-synaptic membrane.
5. The binding opens $\mathrm{Na}^+$ channels; $\mathrm{Na}^+$ diffuses into the post-synaptic neuron, causing depolarisation (EPSP).
6. If threshold is reached (by summation), a new action potential is generated in the post-synaptic neuron.
7. Acetylcholinesterase on the post-synaptic membrane breaks down acetylcholine into choline and acetate, preventing continuous stimulation.

Unidirectional transmission: Only the pre-synaptic terminal has synaptic vesicles (to release neurotransmitter), only the post-synaptic membrane has specific receptors (to detect it), and $\mathrm{Ca}^{2+}$ channels are only on the pre-synaptic side. Therefore, impulses can only travel from pre-synaptic to post-synaptic.

Problem 3: A person's left pupil constricts when light is shone into the right eye, but not when light is shone into the left eye. Explain the normal pathway for the pupillary reflex and identify where the damage is likely to be.

If you get this wrong, revise: Reflex Arcs -- The Pupillary Light Reflex

Solution

Normal pathway (consensual reflex): Light is detected by photoreceptors in the retina. Impulses travel along the optic nerve to the brain, where they reach the optic chiasm. Some fibres cross to the opposite side, while others stay on the same side. Both sets of fibres reach the Edinger-Westphal nuclei (one in each midbrain). From each nucleus, impulses travel along the oculomotor nerve (cranial nerve III) to the circular muscles of the iris in BOTH eyes, causing constriction.

Diagnosis: The consensual reflex works (right eye stimulated causes left pupil to constrict), meaning the pathway from the right retina to the left Edinger-Westphal nucleus and from there to the left iris is intact. However, the direct reflex in the left eye fails (left eye stimulated does not cause left pupil to constrict). This indicates the damage is in the afferent (sensory) pathway of the left eye -- either the left optic nerve or the left retina is damaged. If the efferent pathway (left oculomotor nerve) were damaged, neither the direct nor the consensual reflex would work for the left eye.

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tip

tip Ready to test your understanding of Nervous System? Review the Human Physiology diagnostic test which covers nervous system topics within the DSE specification.

See Diagnostic Guide for instructions on self-marking and building a personal test matrix.

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Drugs and the Nervous System

Alcohol (ethanol):**

• Crosses the blood-brain barrier and affects multiple neurotransmitter systems:
  • Enhances GABA activity (inhibitory neurotransmitter): slows brain function, reduces anxiety, impairs coordination
  • Inhibits glutamate (excitatory neurotransmitter): further depresses brain activity
  • Increases dopamine release in the reward pathway: contributes to addictive potential
• Short-term effects: impaired judgement, reduced coordination, slurred speech, slowed reaction time
• Long-term effects: liver damage (cirrhosis), brain damage, cardiovascular disease, addiction
• Tolerance develops with repeated use: the brain adapts by reducing the number of GABA receptors and increasing glutamate receptors, requiring more alcohol for the same effect

Caffeine:

• Binds to adenosine receptors (without activating them), blocking the inhibitory effect of adenosine
• Adenosine normally promotes sleep and suppresses arousal; blocking it increases alertness
• Increases dopamine release, contributing to mild addictive potential
• Short-term effects: increased alertness, reduced fatigue, increased heart rate
• Long-term effects: tolerance (more receptors produced), withdrawal symptoms (headache, fatigue) when intake stops

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Neurological Disorders

Stroke

A stroke occurs when blood flow to part of the brain is disrupted, causing brain cells to die from oxygen and glucose deprivation.

Type	Cause	Proportion
Ischaemic stroke	Blockage of a brain artery by a blood clot or thrombus	~85%
Haemorrhagic stroke	Rupture of a blood vessel in the brain, causing bleeding and pressure	~15%

Risk factors: High blood pressure, smoking, diabetes, high cholesterol, obesity, age, family history.

Symptoms: Sudden weakness or numbness on one side of the body, slurred speech, confusion, visual disturbances, severe headache, difficulty walking.

Parkinson's Disease

• Degenerative disorder of the central nervous system
• Caused by the death of dopamine-producing neurons in the substantia nigra (part of the basal ganglia in the midbrain)
• Dopamine is essential for initiating and coordinating voluntary movement
• Symptoms: tremor (especially at rest), rigidity, slow movement (bradykinesia), poor balance, difficulty initiating movement
• Treatment: L-DOPA (a dopamine precursor that can cross the blood-brain barrier and is converted to dopamine in the brain); dopamine agonists; deep brain stimulation

Alzheimer's Disease

• Progressive degenerative brain disease and the most common cause of dementia
• Characterised by the accumulation of amyloid plaques (protein deposits between neurons) and neurofibrillary tangles (abnormally phosphorylated tau protein inside neurons)
• Neurons in the cerebral cortex (especially the hippocampus, involved in memory) progressively die
• Symptoms: progressive memory loss, confusion, difficulty with language, personality changes, loss of independence
• No cure; treatment focuses on managing symptoms and slowing progression

Multiple Sclerosis (MS)

• Autoimmune disease in which the immune system attacks the myelin sheath of neurons in the CNS
• Destruction of myelin disrupts the transmission of nerve impulses (slows or blocks conduction)
• Symptoms: vision problems, muscle weakness, spasms, fatigue, coordination difficulties, numbness
• More common in women than men; typically diagnosed between ages 20-40
• Treatment: immunosuppressants, corticosteroids (during relapses), disease-modifying therapies

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Memory and Learning

Types of Memory

Type	Description	Duration	Capacity
Sensory memory	Brief storage of sensory information (visual, auditory, tactile)	Less than 1 second	Very large
Short-term memory (STM)	Temporary storage of information currently being processed; typically holds 7$\pm$2 items	15-30 seconds	Limited (7$\pm$2 items)
Long-term memory (LTM)	Permanent storage of information; potentially unlimited capacity	Days to lifetime	Potentially unlimited

Short-Term Memory

• Information is held as electrical impulses circulating in neural circuits (reverberating circuits)
• Capacity is limited to approximately 7$\pm$2 items (Miller's Law)
• Can be increased by chunking -- grouping individual items into meaningful units (e.g., remembering a phone number as 3 chunks rather than 10 digits)
• Duration can be extended by rehearsal -- actively repeating the information
• Information is easily displaced by new incoming information (proactive and retroactive interference)

Long-Term Memory

Long-term memory is subdivided into:

Type	Description	Example
Explicit (declarative)	Conscious recall of facts and events
-- Episodic memory	Memory of specific personal experiences and events	Remembering your 18th birthday
-- Semantic memory	Memory of general knowledge, facts, concepts	Knowing that Paris is the capital of France
Implicit (non-declarative)	Unconscious memory; skills and procedures that are performed automatically
-- Procedural memory	Memory of motor skills and how to perform tasks	Riding a bicycle, typing on a keyboard
-- Priming	Exposure to one stimulus influences response to a subsequent stimulus	Seeing the word "doctor" makes you faster to recognise "nurse"
-- Classical conditioning	Associative learning; pairing a neutral stimulus with an unconditioned stimulus to produce a conditioned response	Pavlov's dogs salivating at a bell

Memory Consolidation and the Role of Sleep

• Consolidation is the process by which short-term memories are converted into long-term memories
• Occurs primarily during slow-wave sleep (deep sleep, stages 3-4 of NREM sleep) and REM sleep
• The hippocampus plays a central role in memory consolidation -- it acts as a temporary storage site and gradually transfers memories to the cerebral cortex for long-term storage
• During sleep, neural circuits activated during learning are replayed (reactivated), strengthening the synaptic connections (long-term potentiation)
• Sleep deprivation significantly impairs consolidation and learning

Long-Term Potentiation (LTP)

LTP is the cellular basis of learning and memory:

1. A presynaptic neuron repeatedly and persistently stimulates a postsynaptic neuron
2. This causes the release of glutamate (excitatory neurotransmitter), which binds to NMDA and AMPA receptors on the postsynaptic membrane
3. With repeated stimulation, sufficient glutamate is released to activate NMDA receptors (which are normally blocked by a magnesium ion)
4. Calcium ions flow into the postsynaptic neuron through the NMDA receptor channels
5. Calcium triggers a signalling cascade that:
   • Causes more AMPA receptors to be inserted into the postsynaptic membrane (increasing sensitivity to glutamate)
   • Activates gene transcription in the postsynaptic neuron (synthesis of new proteins)
   • Strengthens the synaptic connection between the two neurons
6. The strengthened connection means that future stimulation of the presynaptic neuron produces a larger response in the postsynaptic neuron

Brain Imaging Techniques

Technique	Full Name	Principle	Uses	Resolution
CT scan	Computed Tomography	X-rays are passed through the brain from multiple angles; computer constructs a 3D image from the X-ray data	Detecting tumours, haemorrhages, skull fractures; quick and widely available	Moderate
MRI	Magnetic Resonance Imaging	Strong magnetic field aligns hydrogen nuclei in water molecules; radio waves perturb them; emitted signals form an image	Detailed structural images of the brain; detecting tumours, lesions, atrophy	High
fMRI	Functional MRI	Measures changes in blood oxygenation (BOLD signal) as a proxy for neural activity; active brain areas receive more blood flow	Identifying which brain regions are active during specific tasks or cognitive processes	Moderate-high
PET scan	Positron Emission Tomography	Patient injected with radioactive glucose; scanner detects positrons emitted by decaying radioisotope; active areas consume more glucose	Mapping brain activity; studying brain function in disease (e.g., Alzheimer's, Parkinson's)	Moderate
EEG	Electroencephalography	Electrodes placed on the scalp detect electrical activity (brain waves) produced by neurons	Diagnosing epilepsy; studying sleep stages; monitoring anaesthesia depth	Low temporal resolution (high temporal)

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Synaptic Plasticity

Synaptic Pruning

• During early brain development, the brain produces an excess of neurons and synaptic connections
• Synaptic pruning is the process by which unused or weak synaptic connections are eliminated, while frequently used connections are strengthened
• "Use it or lose it" -- synaptic connections that are rarely activated are removed
• Pruning is guided by experience and neural activity, making the brain more efficient
• Critical periods exist for certain types of learning (e.g., language development, visual processing); if the appropriate input is not received during the critical period, the relevant neural circuits may not develop properly

Neurotransmitters Summary Table

Neurotransmitter	Type	Function	Disorders Associated with Imbalance
Acetylcholine (ACh)	Excitatory (mainly)	Muscle contraction at neuromuscular junctions; role in memory, attention, and arousal in the CNS	Alzheimer's disease (deficiency); myasthenia gravis (receptor destruction)
Dopamine	Both	Reward and pleasure; voluntary movement control; motivation; emotional response	Parkinson's disease (deficiency); schizophrenia (excess in certain pathways)
Serotonin (5-HT)	Both	Mood regulation; sleep; appetite; pain perception; body temperature regulation	Depression (deficiency); anxiety disorders
GABA	Inhibitory	Principal inhibitory neurotransmitter in the brain; reduces neuronal excitability; prevents over-excitation	Epilepsy (reduced GABA activity); anxiety (reduced GABA)
Glutamate	Excitatory	Principal excitatory neurotransmitter in the brain; essential for learning and memory (LTP)	Excitotoxicity (excess glutamate causes neuronal death, implicated in stroke and Alzheimer's)
Noradrenaline (norepinephrine)	Both	Alertness; attention; fight-or-flight response; regulates heart rate and blood pressure	Depression (deficiency); ADHD; anxiety disorders
Endorphins	Inhibitory	Pain relief; euphoria; stress reduction; released during exercise, injury, and excitement	Endorphin deficiency linked to chronic pain and depression

Common Pitfalls

• Students often confuse agonists and antagonists: agonists mimic or enhance the effect of a neurotransmitter; antagonists block its effect
• Curare is an antagonist at acetylcholine receptors at the neuromuscular junction -- it causes paralysis by preventing ACh from binding, but it does NOT affect ACh release
• Parkinson's disease involves dopamine deficiency (not excess); schizophrenia involves dopamine excess (not deficiency)
• GABA is the main inhibitory neurotransmitter, NOT the main excitatory one (that is glutamate)
• Synaptic transmission is always in one direction: presynaptic $\rightarrow$ postsynaptic (because only the presynaptic terminal has synaptic vesicles containing neurotransmitter)