CNS Physiology & Anatomy – Summation, Neurotransmitters, Pathways and Motor Cortex

Graded Potentials & Their Summation

• Every time a presynaptic neuron fires an action potential (AP) it releases neurotransmitter (NT).
• NT diffuses across the synaptic cleft → binds to receptors on the postsynaptic membrane → produces a graded potential (GP).
• Key features of GPs
– Local, decremental, vary in amplitude, depolarising (EPSP) or hyper-polarising (IPSP).
– If multiple GPs occur close enough in space or time they can sum.
• Two summation modes

1. Temporal summation – one presynaptic neuron fires APs in rapid succession; successive GPs fall on top of each other before the first decays, so amplitudes add.

2. Spatial summation – ≥2 presynaptic neurons release NT onto different locations of the same postsynaptic cell; simultaneous GPs algebraically add.
   – EPSPs and IPSPs also add. Example: (+1)+(-1)=0 (net effect cancelled).
   • Why summation matters
   – Only if the combined depolarisation reaches threshold at the axon hillock will a new AP be triggered.
   – Sub-threshold or dominant IPSP activity → no AP → signal is “filtered out.”

Sequence of Information Flow in a Typical Pathway

• Stimulus (e.g., touch) → mechanically-gated channels in dendrites open → GPs generated.
• GPs sum; if threshold reached at axon hillock → AP #1 produced.
• AP propagates along axon → Ca²⁺ influx at terminals → NT exocytosis.
• NT binds next neuron → new GP … repeat.
• Thus pathways = alternating GP (chemical) ↔ AP (electrical) steps.

Neurotransmitters of Focus

• Definition – chemical signal released by neuron that acts through a receptor at chemical synapse. Stored in vesicles; secretion triggered by AP-mediated Ca²⁺ entry.

1. Acetylcholine (ACh)

• Very abundant; crucial for neuromuscular junction, autonomic ganglia, learning, memory.
• Receptors = cholinergic
– Nicotinic (ionotropic)
• Direct ligand-gated cation channel.
• Always excitatory → EPSP (Na⁺ influx).
– Muscarinic (metabotropic, G-protein)
• Indirect/2ⁿᵈ-messenger.
• Subtype-dependent: some excitatory, some inhibitory (e.g., M₂ in heart → IPSP).

2. Norepinephrine (NE)

• Biogenic amine (modified amino acid). Linked to arousal, euphoria, autonomic sympathetic division.
• Receptors = adrenergic (α, β)
– Can be excitatory or inhibitory.
– Ionotropic or metabotropic depending on subtype.

(Other transmitters – dopamine, serotonin, histamine – acknowledged but not test-focus.)

Synaptic Receptors

• Two functional classes

1. Ionotropic (channel-linked / ligand-gated)
   – Receptor is an ion channel; NT binding → channel opens → immediate but brief ion flux → GP.
   – EPSP: Na⁺/Ca²⁺ in. IPSP: Cl⁻ in or K⁺ out.

2. Metabotropic (G-protein / 2ⁿᵈ messenger)
   – Receptor coupled to intracellular G-protein. Steps:
   • NT binds receptor → conformational change.
   • G-protein exchanges GDP→GTP, moves to activate membrane enzyme (e.g., adenylyl cyclase).
   • Enzyme converts ATP → cAMP (typical 2ⁿᵈ messenger).
   • cAMP opens or closes separate ion channels, modulates enzymes, or alters gene expression.
   – Indirect, slower, longer lasting, amplifiable effects.

Neuronal Pools & Circuit Patterns

• Serial vs parallel processing.
• Basic circuit configurations
– Diverging (one → many).
– Converging (many → one).
– Reverberating (feedback loop; rhythm generation e.g., respiratory center).
– Parallel after-discharge, etc.
• Functional importance – integration, distribution, modulation of signals.

Developmental Anatomy of CNS

• Embryo: ectoderm folds to create neural tube (hollow, fluid-filled).
• Primary vesicles → secondary vesicles → adult structures
– Telencephalon → cerebrum (cerebral hemispheres).
– Diencephalon → thalamus, hypothalamus, epithalamus.
– Mesencephalon → midbrain.
– Metencephalon → pons & cerebellum.
– Myelencephalon → medulla oblongata.
• Differential growth + confinement by skull → brain flexures & cortical folding (gyri/sulci) to maximise surface area.

White vs Gray; Tracts vs Nerves; Nuclei vs Ganglia

• White matter – myelinated axons. Gray matter – somata, dendrites, unmyelinated axons.
• Tract = bundle of CNS axons; nerve = bundle of PNS axons.
• Nucleus = cluster of neuron cell bodies in CNS; ganglion = cluster in PNS.

Ventricular System & CSF Flow

• Hollow remnants of neural tube → ventricles (lat → 3ʳᵈ → cerebral aqueduct → 4ᵗʰ) → central canal.
• Ependymal cells (often ciliated, tight-junctioned in choroid plexus) secrete cerebrospinal fluid (CSF).
• CSF exits 4ᵗʰ ventricle via lateral & median apertures → subarachnoid space → reabsorbed into venous sinuses.

Surface Anatomy: Gyri, Sulci, Fissures

• Gyrus (pl. gyri) – ridge. Sulcus (sulci) – shallow groove. Fissure – deep groove.
• Key landmarks
– Central sulcus: separates frontal & parietal lobes; borders pre- & post-central gyri.
– Lateral sulcus: separates temporal lobe.
– Longitudinal fissure: separates R/L hemispheres.
– Transverse fissure: cerebrum vs cerebellum.

Cerebral Lobes & Basic Functions (preview)

• Frontal – voluntary motor, planning, personality, decision-making.
• Parietal – somatosensory perception & integration.
• Occipital – vision.
• Temporal – audition, memory, language comprehension.
• Insula (deep) – taste, visceral sensation, emotional context.

Motor Areas of the Frontal Lobe

• All voluntary motor cortex is anterior to central sulcus. Components:

Primary Motor Cortex (M1) – Precentral Gyrus

• Contains large pyramidal cells whose axons form the corticospinal (pyramidal) tracts.
• Stimulation → contralateral muscle contraction.
• Topographical map = motor homunculus:
– Medial–inferior M1 → toes, legs.
– Superior → trunk, shoulder.
– Lateral-superior → hand/fingers.
– Lateral-inferior → face, tongue.
– Amount of cortex ∝ fine motor control degree.

Premotor Cortex

• Anterior to M1; stores learned motor skills, plans movements, coordinates several muscle groups; sends program to M1. Receives cerebellar feedback for on-the-fly correction.

Broca’s Area

• Inferior-lateral frontal lobe (dominant hemisphere only).
• Motor program for speech production. Lesion → Broca’s (expressive) aphasia: understand language but cannot articulate words (can still write or sign).

Frontal Eye Field

• Controls voluntary eye movements; keeps gaze tracking objects.

Clinical & Practical Connections

• Summation principles explain how drugs/toxins modulate CNS excitability (e.g., sedatives ↑ IPSP summation).
• Receptor subtype dictates drug action: nicotinic agonists excite everywhere, muscarinic antagonists block slower parasympathetic responses, β-blockers inhibit specific adrenergic targets.
• Knowledge of tracts vs nerves critical for localising lesions (upper vs lower motor neuron signs).
• CSF obstruction at apertures → hydrocephalus.
• Broca’s vs Wernicke’s aphasias differentiate motor vs sensory language cortical regions.