Neurophysiology

The Neuron: Structure and Function

The neuron is the fundamental signalling unit of the nervous system. A typical multipolar neuron consists of: the cell body (soma), containing the nucleus and protein synthesis machinery; dendrites, which receive incoming signals; and the axon, which transmits signals to other neurons or effector cells. At the axon terminal, synaptic vesicles release neurotransmitters into the synaptic cleft. Many axons are myelinated by oligodendrocytes (CNS) or Schwann cells (PNS), increasing conduction velocity via saltatory conduction between Nodes of Ranvier.

The Resting Membrane Potential

At rest, the membrane potential of a typical neuron is approximately −70 mV (inside negative relative to outside). This resting potential results from: (1) differential ionic permeabilities — the membrane is most permeable to K⁺ at rest (via leak channels); (2) concentration gradients established by the Na⁺/K⁺-ATPase; (3) intracellular negatively charged proteins. The Nernst equation calculates the equilibrium potential for each ion. The Goldman-Hodgkin-Katz equation gives the actual resting potential considering the relative permeability of Na⁺, K⁺, and Cl⁻. E_K ≈ −90 mV; E_Na ≈ +60 mV; resting V_m ≈ −70 mV (closer to E_K, reflecting high K⁺ permeability).

Action Potentials

An action potential (AP) is an all-or-none electrical signal generated when the membrane potential reaches threshold (approximately −55 mV). Phases:

1. Depolarisation: voltage-gated Na⁺ channels open rapidly, Na⁺ rushes in (V_m rises toward +30 mV).
2. Repolarisation: Na⁺ channels inactivate (h-gate closure); voltage-gated K⁺ channels open, K⁺ flows out.
3. Hyperpolarisation (after-hyperpolarisation): K⁺ channels close slowly, V_m transiently dips below resting potential.
4. Return to resting potential: via K⁺ channel closure and ongoing Na⁺/K⁺-ATPase activity.

The refractory period limits AP frequency: the absolute refractory period (Na⁺ channels inactivated — no AP possible) and relative refractory period (larger-than-threshold stimulus can elicit an AP). APs are propagated along the axon unidirectionally. In myelinated axons, APs jump from node to node (saltatory conduction), reaching speeds of 70–120 m/s.

Synaptic Transmission

At chemical synapses, APs trigger Ca²⁺ influx through voltage-gated Ca²⁺ channels at the axon terminal, causing exocytosis of neurotransmitter-containing vesicles. Neurotransmitter diffuses across the synaptic cleft (~20 nm) and binds postsynaptic receptors.

Ionotropic receptors (ligand-gated ion channels — AMPA, NMDA, GABA_A, nAChR): produce fast, direct changes in membrane conductance.

Metabotropic receptors (G protein-coupled — mGluR, GABA_B, muscarinic): produce slower, modulatory effects via second messengers.

Excitatory postsynaptic potentials (EPSPs): depolarising (e.g., glutamate via AMPA). Inhibitory postsynaptic potentials (IPSPs): hyperpolarising or shunting (e.g., GABA via GABA_A, opening Cl⁻ channels). Temporal and spatial summation of EPSPs and IPSPs at the axon hillock determines whether an AP is generated. Neurotransmitter is terminated by reuptake, enzymatic degradation (e.g., AChE for ACh, MAO for catecholamines), or diffusion.

The Autonomic Nervous System

The ANS regulates visceral functions (heart rate, glandular secretion, GI motility, vascular tone) involuntarily. It has two main divisions:

Sympathetic (thoracolumbar T1–L2): "fight-or-flight." Short preganglionic fibres (ACh → nAChR in ganglia); long postganglionic fibres release noradrenaline (NA) onto α- and β-adrenergic receptors. Exception: adrenal medulla (receives preganglionic directly, releases adrenaline into blood). Effects: ↑HR, ↑BP, bronchodilation, pupil dilation, glycogenolysis, reduced GI motility.

Parasympathetic (craniosacral CN III, VII, IX, X; S2–4): "rest-and-digest." Long preganglionic fibres (ACh → nAChR at ganglia near/in target organ); short postganglionic fibres release ACh onto muscarinic (M) receptors. Effects: ↓HR, bronchoconstriction, ↑GI motility, pupil constriction, bladder contraction.

Reflex Arcs

A reflex is a rapid, involuntary, stereotyped motor response to a specific sensory stimulus. A basic reflex arc consists of: (1) receptor — detects stimulus; (2) afferent neuron — sensory signal to CNS; (3) integrating centre — spinal cord or brainstem; (4) efferent neuron — motor signal; (5) effector — muscle or gland. The monosynaptic stretch reflex (e.g., knee-jerk/patellar reflex) involves only one synapse: Ia afferent from muscle spindle synapses directly on α-motor neuron. Polysynaptic reflexes involve interneurons and allow more complex integration, such as the withdrawal (flexor) reflex.