Neurophysiology (updated)

Cerebrum components

• Cerebral cortex (outer grey matter)

• Cortical white matter (inside cortex)

• Deep grey nuclei (basal ganglia)

• Amygdala and hippocampus

*hemispheres joined by corpus callosum

Cerebellar cortex

Rear region, deeply folded lobes, highest neuron density in CNS

• 3 layers of outer grey matter)

  • Molecular (synaptic)

  • Purkinje (single dark row of neurons)

  • Granular (synaptic)

• Inner white matter (deep to granular, inside grey layers)

Cerebral cortex components (6 layers)

Outer I → molecular
II → external granular
III → pyramidal
IV → inner granular
V → ganglionic (dendrites, pyramidal neurons)
Inner VI → multiform (afferent & efferent fibres, axons)

Neuron cytoskeleton components

1. Microtubules: long hollow tubes, maintain shape, transport, found in soma and axon)

2. Neurofilaments (primary type of intermediate filament): structural support, maintain diameter, found in axon)

3. Actin filaments (aka microfilaments): thin flexible fibres, cell movement, shape, synaptic connections, hence found in dendrites,axon terminal, and axon

2 common forms of cytoarchitecture

Nuucleus (nuclei) → clusters of similar neuron types OR a collection of a few neuronal cell types, like the nucleus basalis

Lamina (laminae) → layers like in the cerebral cortex

ALSO: ganglia & columns

Foramen magnum

‘Great hole’, a large oval shaped opening in the occipital bone of the neurocranium

Upper vs lower motor neurons

Upper → stimulate lower, send info to the spinal cord, located in cerebral cortex

Lower → stimulate muscles, located in spinal cord with axons in PNS

Brainstem

1. The medulla oblongata (myelencephalon) + pons (bridge/metencephalon)

   • Has the motor neurons acting on the head and neck

   • Primitive reflexes, involuntary functions (BP, HR), wakeful/consciousness

2. The midbrain (mesencephalon)

   • Head orientating and eye movements

   • Integration of complex/smooth movement, proprioception

     → modulates axonal pathways between spinal cord, cortex, and cerebellum

The cerebellum

‘Little brain’, but has 50% of brain’s total neurons

• 2 deeply folded hemispheres

• Complex motor skills

  → coordination, balance, posture, motor learning, memory

Diencephalon

1. Thalamus → grey matter area, gateway for senses, consciousness, sleep memory

2. Hypothalamus → coordinates & integrates endocrine, autonomic, homeostatic functions

3. Subthalamus → basal nucleus, motor planning, smooth movement

4. Epithalamus → pineal gland, circadian rhythm

Cerebrum

Provides ‘actual’ cognitive awareness

1. Cerebral cortex (grey matter) → all the lobes, 6 neuron layers I-VI

2. Cortical white matter

3. Basal ganglia (deep grey nuclei)

4. Amygdala & hippocampus

Gyri vs sulcus vs fissures

Gyri = hills

Sulcus = shallow grooves

Fissures = deep grooves

5 lobes and their functions

1. Occipital lobe (V1) → visual processing, organisation of visual field

2. Parietal lobe (S1) → primary somatosensory, language, multi-sensory integration, touch, pain, temperature *postcentral gyrus

3. Frontal lobe (M1)→ speech, language, emotion, memory, judgment, personality, problem-solving, the homunculus *precentral gyrus

4. Temporal lobe (A1)→ auditory information processing, speech, language, part of limbic system

5. Insular lobe (G1) → gustatory and sensoriomotor processing, risk-reward behaviour, interception, visceral pain states, empathy

Neocortex

90% of the cerebral cortex, comes later evolutionarily, most evolved part of the brain and is responsible for higher-order brain functions

• Sensory perception

• Motor commands

• Cognitive functions

• Language

• Conscious thought

Key components of the emotional motor system

Expression of emotion:

• Hypothalamus

• Cingulate

• Amygdala

• Prefrontal cortex

Emotional memory:

• Hippocampus

• Amygdala

• Thalamus

• Prefrontal cortex

+ insular cortex

Spinal cord main features

Vertebral canal (bone) + 2 symmetrical spinal cords (sensory & motor)
→ sensory axons (PNS to CNS) have afferent dorsal roots
→ motor axons (from CNS to PNS) have efferent ventral roots

• Central canal filled with CSF

• Butterfly of grey matter (2 dorsal and 2 ventral)

• 31 segments (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal)

• Sensory

• Vertebral canal is longer than spinal cord (roots below L1/2 are the horse tail/cauda equina)

Dorsal, ventral & lateral horns of spinal cord

Dorsal horn → 2nd order sensory neurons, receives information from 1st order entering dorsal root

Ventral horn → lower motor neurons, sends axons into ventral root to muscle

Lateral horn → autonomic motor neurons, sense axons to autonomic ganglia

Types of ascending (sensory) axon tracts

1. Spinothalamic tract: pain, temperature, crude touch, sensory information

   • Decusses at the anterior white commissure (contralateral), ascends to thalamus

   • 1st sensory neuron in dorsal root ganglia

   • 2nd sensory neuron in dorsal horn

2. Dorsal column: discriminative/fine touch, proprioception

   • Ascends through 2 parallel tracts (ipsilateral), first synapsing at either:
     → gracile nucleus (lower body)
     → cuneate nucleus (upper body)

   • 1st order crosses the medial lemniscus

   • 2nd order ascends to the thalamus

Types of descending (motor) axon tracts

Lateral corticospinal tract: carries upper motor neurons from cerebral cortex, motor control both conscious (upper) and basic (lower)

• Upper motor neuron soma are in the primary motor cortex (frontal lobe)

• Lower motor neuron soma are in the ventral horn of spinal cord grey matter

• Decusses at the medulla (contralateral), synapsing with motor neurons in the white matter of the ventral horn

Flow of CSF

1. Produced in the choroid plexus (mostly in the lateral ventricles)

   ↓ Interventricular foramina

2. Third ventricle

   ↓ Cerebral aqueduct

3. Fourth ventricle

   ↓ Foramina of Luschka & Magendie

4. Subarachnoid space

   ↓ Arachnoid wall

5. Superior saggital sinus

   ↓ Venous circulation

6. Heart

Brain ventricles

2 lateral: under corpus callosum, 1 in each hemisphere, has 2 apertures, the ‘foramina of Luschka’

Third ventricle: Flat, sits between the thalami (diencephalon), uses the cerebral aqueduct

Fourth ventricle: Cerebellum as the roof, pons & part of the medulla as the floor, is diamond shaped, uses a median aperture, the ‘foramina of Magendie’

The meninges

1. Dura mater: ‘tough mother’, the outer layer

   • ‘Falx cerebri’ flap separates L and R hemispheres

   • ‘Tentorium cerebelli’ crescent fold separates cerebellum from central hemisphere

   • 2 layers separate to form the dural sinus

2. Arachnoid mater: 'spidery’, a weblike appearance filled with CSF

   • CSF leaks out ventricle aperatures to fill the arachnoid bag

   • Tethers blood vessels

   • Arachnoid granulations pierce the dural sinus and leak CSF

3. Pia mater: ‘gentle mother’, follows gyri and sulci

   • Note: the subarachnoid space sits between the pia mater and arachnoid mater

Peripheral nerve structure

Axons (endoneurium) bundle into fascicles (perineurium)
→ Fasicles bundle into nerves (epineurium)
→ Surrounded by connective tissue (+ fat and vasculature)

Sensory nerve receptor types

• Mechanoreceptors

  • Mechanical pressure or distortion

  • Free nerve endings OR structures (Meissner’s/Pacinian corpuscles)

• Thermoreceptors

  • Changes in temperature

  • Free nerve endings in skin (separate hot/cold receptors)

• Nociceptors

  • Pain from physical damage or inflammation

  • Free nerve endings in skin, muscles, internal organs

• Photoreceptors

  • Detect light

  • Retina of eye (rods for light and cones for colour)

• Chemoreceptors

  • Detect chemical stimuli

  • Specialised cells (tastebuds, olfactory receptors)

• Proprioceptors

  • Position and movement of body

  • Muscles, tendons, joints like muscle spindles/Golgi tendon organs

Ramus

When dorsal and ventral roots merge into nerves and redivide categorised by location

• Dorsal primary ramus = muscles of skin and back

• Ventral primary ramus = anterolateral parts of the trunk and limbs

Types of somatic motor nerves

1. Cranial nerves → motor neurons originating in the brainstem (12 pairs)

2. Spinal nerves → motor neurons originating in the spinal cord (31 pairs)

Motor endplates

AKA neuromuscular junctions

Specialised structures where motor neurons connect with skeletal muscle fibres, transmitting signals to cause muscle contractions

Consists of: presynaptic terminal, synaptic cleft, postsynaptic membrane

Spinal nerve vs plexus

A network of intersecting nerves, redistributing nerve fibres to specific body regions

Rami
↓
Superior + middle + inferior trunks
↓ converge
Posterior, medial & lateral cords
↓ split
5 terminal branches

CN I

Olfactory nerve

Modalities: special sensory

Innervations: olfactory mucosa

Pathway:
Receptors in olfactory epithelium
↓ Through cribiform plate
Primary neurons synapse in olfactory bulbs
↓ Secondary neurons relay stimuli through olfactory tract
Olfactory cortex

CN II

Optic nerve

Modalities: special sensory

Innervations: retina

Pathway:
Rods and cells send electrical signals to retinal ganglion cells
↓ Form optic nerves
Leave the eye at optic disc (blind spot)
↓ Optic nerves merge and decussate at optic chiasm
Fibres continue as optic tracts
↓ Cross midline before entering CNS
To diencephalon (LGN)

CN III

Oculomotor nerve

Modalities: Somatomotor and visceral motor (efferent)

Innervations:
MOTOR controls 4/6 of orbital
Superior rectus = elevates and intorts (top of eye inward)
Medial rectus = adducts (moves medially)
Inferior rectus = depresses and rotates medially
Inferior oblique = elevates and rotates laterally

VISCERAL controls ciliary muscles (focus) & pupillary sphincter (aperture)

Pathway:
Oculo motor nucleus (midbrain)
↓ Exits via interpeduncular fossa
Into cavernous sinus
↓ Superior orbital fissure
Eye orbit

CN V

Trigeminal nerve

^3 divisions

Modalities: somatomotor and somatosensory

Innervations:
V1. Opthalamic = forehead, upper eyelid, nose [sensory]
V2. Maxillary = cheek, lower eyelid, nose, upper gums/teeth [sensory]
V3. Mandibular = chin, lower lip, lower gums/teeth, anterior 2/3 tongue [sensory AND motor]

Pathway:
3 divisions converge at the trigeminal ganglion (1^o neurons)
↓ Through sensory root (larger of 2) and projects to trigeminal nuclei (pons)
Ends up in the thalamus (VPM nucleus)

AND

Brainstem (pons)
↓ Fibres emerge from lateral surface, medial
Passes through trigeminal ganglion without synapsing
↓ Joins mandibular nerve exiting the foramen ovale
Innervates mastication muscles

CN VII

Facial nerve

Modalities: ALL sensory modalities

Innervations:
Special sensory = taste on anterior 2/3 tongue (chorda tympani branch)
Somatosensory = external ear, posterior scalp, auricle
Somatomotor = facial expressions, stapedius, speech, swallowing
Visceral sensory = outer ear canal, tympanic membrane, pinna
Visceral motor = tear & salivary glands (lacrimal, submandibular, sublingual, nasal, palatine)

Pathway:
Specialised nuclei (pons), a motor + sensory root
↓ Exits at pontomedullary junction
Joined with vestibulocochlear, enters internal acoustic meatus (bone canal)
↓ Enters mastoid part of facial canal
Sensory nerve soma are located at geniculate ganglion

EXTRACRANIALLY:
Enters parotid gland
↓ divides into terminal branches for facial expression
Temporal, zygomatic, buccal, marginal mandibular, cervical

CN VIII

Vestibulocochlear nerve

Modalities: Special sensory

Innervations: Vestibular system (inner ear), cochlea (hearing)

Pathway:
Inner ear
↓ Internal acoustic meatus (bone canal)
Splits into vestibular & cochlear nerves…

1. Forms spiral ganglion → cochlear nuclei in brainstem

2. Connects to vestibular ganglion → vestibular nuclei in brainstem

CN IX

Glossopharyngeal nerve

Modalities: ALL sensory modalities

Innervations:
Special sensory = taste on posterior 1/3 of tongue
Somatosensory = Oropharynx, palatine tonsils, posterior 1/3 tongue, tympanic membrane, eustachain tube
Somatomotor = Stylopharyngeus muscle (swallowing)
Visceral sensory = Carotid sinus (blood pressure), carotid body (breathing)
Visceral motor = Parotid gland (saliva) by innervating salivary nucleus

Pathway:
Medulla (postolivary sulcus)
↓ exits jugular foramen
Descends neck to innervate

CN X

Vagus nerve
Modalities: ALL sensory modalities

Innervations:
Special sensory = taste, epiglottis, esophagus, roof, pharynx, larynx
Somatosensory = Pharynx, larynx, abdominal viscera
Somatomotor = Swallowing (pharynx, larynx, soft palette)
Visceral sensory = Heart, lungs, abdominal viscera
Visceral motor = Gastrointestinal tract, heart, bronchi

Pathway:
Medulla (posterolateral sulcus)
↓ Exits jugular foramen
Descends neck in carotid sheath
↓ Into chest and over pericardium
Branches throughout abdomen

CN XI

Accessory nerve

Modalities: Somatomotor

Innervations: Sternocleidomastoid (rotate head), trapezius (tilt/back head, shoulders)

Pathway:
[spinal root], C1-C6 for 2 muscles
↓ Emerges laterally, ascends foreman magnum
Joins cranial root
↓ Descends to sternoclemidomastoid
Cervical fascia of posterior neck triangle

[cranial root], Medulla (nucleus ambiguus)
↓ Through posterior cranial fossa
Joins spinal root
↓ Separate after jugular foramen
Joins vagus to innervate palate, pharynx, larynx

CN XII

Hypoglossal nerve

Modalities: Somatomotor

Innervations: Most tongue muscles (all intrinsic, most extrinsic)

Pathway:
Medulla (hypoglossal nucleus)
↓ Exits ventrolateral sulcus
Across posterior cranial fossa
↓ Hypoglossal canal (in occipital bone)
Through neck to tongue

Dorsal vs ventral surface of spinal cord

Ventral has the anterior spinal artery, along ventral median fissire

• Both have rootlets joining to roots, then nerves

• Dorsal root has a bump (DRG = sensory neuron soma) and the dorsal median sulcus

• Ventral (anterior) has vertebral spines

• Dorsal (posterior) has vertebral bodies

Denticulate ligaments

Pia mater adherence to the spinal cord, forming triangular extensions along the lateral margin, also tethers to dura mater

Conus medullaris

Tapering of the caudal end of the spinal cord and anchored to the vertebral column with the filum terminal

→ spinal cord ends at junction of LV1/LV2
→ surrounded by the cauda equina (bundles of loose nerve rootlets for pelvis and lower limbs)

Sequence of vertebrae sections from rostral to caudal

Cervical → thoracic → lumbar → sacral → coccygeal

Note on vertebral levels

C1-7 exit intervertebral foramen above their vertebral level

C8 and downwards exit above throacic vertebra 1

Cervical and lumber enlargement

Thickening of the spinal cord to carry more LMN to supply information to the upper and lower limbs

Lateral horns

T1-L2 segments

Contain soma of LMN AKA (preganglionic) visceral motor neurons
→ to sympathetic ganglia, sympathetic fight or flight

Lateral corticospinal tract

Descending, somatomotor, ventral
→ Contralateral, voluntary motor movement
→ Cerebral cortex to spinal cord

1. UMN from primary motor cortex decussates at medulla (pyramidal motor decussation)

2. Travels down the corticospinal tract

3. Synapses with a LMN in the ventral horn

Spinothalamic tract

Ascending, somatosensory, dorsal
→ Contralateral
→ Pain, temperature, crude touch

1. DRG neurons synapse in the dorsal horn with 2^o neurons

2. 2^o neurons decussate at the anteiror white commisure and ascend in the ventrolateral portion of spinal cord white matter

3. Ascends to hypothalamus

Dorsal column tracts

Ascending, somatosensory, dorsal

→ gracile fasciculus (lower body, <T6) & cuneate fasciculus (upper body, >T6)
→ ipsilateral, fine touch, vibration, proprioception

1. 1^o neuron enters through DRG and ascends in either tract

2. Synapses in the medulla in either cuneate/gracile nucleus

3. 2^o neuron decussate forming the medial lemniscus, and ascend to the thalamus

Resting membrane potential

The difference in electrical potential between the intracellular space of a neuron (-65 to -70 mV) and outside the cell

→ due to a phospholipid bilayer, impermeable to ions (aq)

Pumps vs channels

Pumps are proteins that ACTIVELY transport ions against their concentration gradient, requiring energy (Na/K and Ca)

Vs

Channels are proteins that allow certain ions to move across membrane = rapid movement, contributing to mV and APs

• Voltage-gated = open/close in response to changes in mV

• Ligand-gated = open/close in response to NT binding

• Leak channels = always open, passive flow
  

Steps of an action potential

1. Neuron is at resting membrane potential

2. Depolarising stimulus arrives (NT or change in mV)

3. Membrane depolarises to threshold → VGSC open & Na enters

4. Rapid Na entry depolarises the cell

5. At peak, VGSC close and VGPC open gradually in response to depolarisation

6. Potassium moves from cell to extracellular fluid

7. K channels remain open, and additional K anions leave the cell, hyperpolarising it

8. VGPC close, and rate of K leakage reduces

9. Cell returns to RMP and resting ion permeability

Significance of a neuron reaching threshold

Synaptic potentials (EPSPs and IPSPs) are graded, and can summate to reach threshold, where a neuron is depolarised enough to trigger an all-or-nothing action potential, and open VGSCs.

Why are action potentials are said to be ‘all or none’?

Once threshold stimulus is reached, an AP will occur fully, versus not at all. The AP propagates along the neuron without a decrease in magnitude

Significance of the axon hillock in APs

• Integration centre: for all the inhibitory & excitatory signals received at the synaptic bouton (dendrites and cell body)

• Threshold determination: high VGSC density = high sensitivity to changes in mV, it’s easiest to begin an AP here

• Initiation: AP propagates from here, down the axon to other neurons or muscles

Absolute and relative refractory periods (+ physiological basis)

Action potential
↓
Absolute refractory period = impossible to fire more APs, as the VGSCs are either open, opening, or inactivated (prevents reverberation)
↓
Relative refractory period = Harder than usual to drive an AP, only with a bigger depolarising stimulus. Some VGPCs are still open, causing hyperpolarisation.

Myelinated vs non myelinated axons

APs face the following issues during propagation:

1. Loss of local circuit through ion leakage channels

2. Axoplasmic resistance against depolarising currents (axon size)

3. Electrical resistance (discharging of large charges on membrane)

Unmyelinated axons:

• AP can only propagate on membranes with high VGSC density

• Each channel has to slowly be sequentially depolarised

• Can go in the reverse direction, as refractory period is shorter

Myelinated axons

• Myelin blocks leakage of current between nodes of ranvier

• Myelin insulates the axon to prevent charge buildup and current can easily spread to next node (no resistance)

• Propagation is much faster as AP can jump to VGSCs in nodes

• Less ion exchange = more energy efficient

Synaptic structure and function

Presynaptic neuron → recieves a propagating AP, and opens VGCC, allowing Ca²⁺ to enter the cell

• Synaptic vesicles: sacks filled with NT

• Axon terminal: NT vesicles are released into synaptic cleft in response to depolarisation

↓

Synaptic cleft: gap ~20-40 nm → NT diffuses across cleft to postsynaptic neuron

↓

Postsynaptic neuron: has receptor proteins for diffusing NTs to bind to, intiating a response
→ ion channels on the postsynaptic membrane open/close, changing its mV to excite or inhibit this neuron

Steps of synaptic transmission

1. AP arrival down the axon of the presynaptic neuron

2. CGCCs open and influx of calcium occurs to depolarise

3. Depolarisation triggers synaptic vesicle release and fusion with the presynaptic membrane to release into synapic cleft

4. NTs diffuse across cleft and bind to speific receptors on postsynaptic membrane

5. Post synaptic rexponse → NT binding can open/close ion channels, changing the postsynaptic neuron’s membrane potential (excitation OR inhibition)

6. NT action is terminated via: reuptake into presynaptic neuron, enzyme degredation, diffusion away from synapse

Synaptic potential summation

Multiple inputs contributing to neuron mV threshold

• Temporal summation: when multiple APs arrive at a single synapse in rapid succession leading to a larger change in mV

• Spatial summation: when multiple PSPs from different synapses combine if close enough in time and space → each release NTs at different synapses on the same neuron

What ions are responsible for determining mV in resting conditions?

Intracellular: K⁺, Org^-

Extracellular: Na⁺, Cl^-

Resting membrane potential (V_m) vs Equilibrium potential (in excitable cells)

E_ion [given by Nernst equation]: membrane potential at equilibrium, when no ions are flowing in and out of a (hypothetical) cell (only permeable to one ion)

V_m: The steady-state difference in voltage when the cell is at rest, determined by the relative permeabilities and concentrations of K, Na & Cl

CN IV

Trochlear nerve
[only CN to emerge posterior/dorsal on brainstem]

Modalities: Somatomotor

Innervations: Superior oblique muscle (rotating eye down, laterally)

Pathway:
Midbrain
↓ Cavernous sinus
Superior orbital fissure
↓ Enters orbit
Superior oblique muscle

CN VI

Abducens nerve

Modalities: Somatomotor

Innervations: Lateral rectus muscle (abduction)

Pathway:
Pons
↓ Exits brainstem
Pontomedullary junction
↓ Subarachnoid space
Cavernous sinus to innervate