Neurophysiology

The nervous system is the body's communication and control network — receiving information from the environment, processing it, and coordinating rapid responses. It is divided into two main parts: Central nervous system (CNS): - Brain — the master controller: processes sensory information, generates thoughts and emotions, coordinates voluntary movement, stores memories, and regulates homeostasis (via the hypothalamus) - Spinal cord — the main highway between brain and body; also processes simple reflexes independently of the brain Peripheral nervous system (PNS): - Somatic nervous system — voluntary control of skeletal muscles; carries sensory information (pain, touch, proprioception) from the body to the brain - Autonomic nervous system (ANS) — involuntary control of smooth muscle, cardiac muscle, and glands: - Sympathetic — "fight or flight" response (increases heart rate, dilates pupils, inhibits digestion) - Parasympathetic — "rest and digest" (slows heart, stimulates digestion, constricts pupils) The fundamental unit of the nervous system is the neuron (nerve cell). The human brain contains approximately 86 billion neurons, each forming thousands of connections. Understanding how a single neuron works is the key to understanding the entire system.

The ability of neurons to transmit signals depends on an electrical voltage across their membrane — called the resting membrane potential. At rest, the inside of a neuron is negatively charged relative to the outside, by about −70 millivolts (mV). This charge difference is maintained by: 1. Unequal ion distribution: - Inside the cell: high potassium (K⁺), high negatively-charged proteins, low sodium (Na⁺), low chloride (Cl⁻) - Outside the cell: high sodium (Na⁺), high chloride (Cl⁻), low potassium (K⁺) 2. Selective permeability of the membrane: At rest, the membrane is much more permeable to K⁺ than to Na⁺. K⁺ leaks slowly out of the cell (following its concentration gradient), carrying positive charge out → leaving the inside more negative. 3. The sodium-potassium pump (Na⁺/K⁺-ATPase): This membrane protein actively pumps 3 Na⁺ OUT and 2 K⁺ IN for every cycle — using ATP energy. This continually maintains the ion gradients. It also contributes directly to the negative resting potential (pumps out more positive charge than it brings in). Why this matters: The −70 mV resting potential is like a cocked gun — the neuron is poised to fire. All neuronal signalling depends on temporarily reversing this charge, then restoring it. Anything that disrupts the Na⁺/K⁺ pump (oxygen deprivation, cardiac arrest) immediately causes neurons to fail — which is why brain damage occurs within minutes of cardiac arrest.

When a neuron is sufficiently stimulated, it generates an action potential — a brief, explosive reversal of the membrane potential that travels along the neuron at high speed. This is the fundamental unit of neural communication. The action potential has distinct phases: 1. Resting state (−70 mV) Voltage-gated Na⁺ and K⁺ channels are closed. The resting potential is maintained. 2. Depolarisation (threshold) A stimulus causes the membrane potential to rise. If it reaches the threshold (about −55 mV), voltage-gated Na⁺ channels snap OPEN. Na⁺ floods INTO the cell rapidly (following its concentration and electrical gradients) → inside becomes less negative, then positive. Membrane potential swings to about +30 mV. This is depolarisation — the inside is now positive. 3. Repolarisation Na⁺ channels automatically inactivate after about 1 ms. Meanwhile, voltage-gated K⁺ channels open → K⁺ flows OUT of the cell (following its gradient) → inside becomes negative again. Membrane returns towards −70 mV. 4. Hyperpolarisation (refractory period) K⁺ channels close slowly → K⁺ leaks out a fraction too long → membrane briefly overshoots to about −80 mV. The neuron cannot fire again during this time (absolute refractory period while Na⁺ channels are inactivated). This ensures signals travel in one direction only. 5. Restoration Na⁺/K⁺ pump restores the ion gradients → back to −70 mV. All-or-nothing principle: An action potential either happens fully or not at all — there is no "weak" action potential. The strength of a signal is encoded by the FREQUENCY of action potentials, not their size. More stimulation = more action potentials per second. Speed of conduction: Action potentials travel faster in neurons with myelin — a fatty insulating sheath around the axon. Myelin allows the signal to "jump" between gaps in the myelin (nodes of Ranvier) rather than propagating continuously — called saltatory conduction. Myelinated neurons conduct at 70–120 m/s; unmyelinated at 0.5–2 m/s. Multiple sclerosis (MS) is caused by immune destruction of myelin → slowed or blocked nerve conduction → symptoms: weakness, numbness, visual disturbance, coordination problems.

Neurons don't directly touch each other — they communicate across tiny gaps called synapses. The sending neuron is the presynaptic neuron; the receiving neuron (or muscle cell) is the postsynaptic neuron. How a synapse works: 1. An action potential travels down the axon of the presynaptic neuron to the axon terminal (synaptic knob) 2. The action potential triggers the opening of voltage-gated Ca²⁺ channels in the terminal 3. Ca²⁺ rushes in → causes synaptic vesicles (membrane-bound packages of neurotransmitter) to fuse with the cell membrane and release their neurotransmitter into the synaptic cleft (the gap) 4. Neurotransmitter molecules diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane 5. Binding opens ion channels in the postsynaptic membrane → either excitatory (depolarises the postsynaptic cell, making it more likely to fire) or inhibitory (hyperpolarises it, making it less likely to fire) 6. Neurotransmitter is removed from the cleft by: reuptake into the presynaptic neuron (recycling), enzymatic degradation, or diffusion away Key neurotransmitters: - Glutamate — the main excitatory neurotransmitter in the CNS - GABA (gamma-aminobutyric acid) — the main inhibitory neurotransmitter. Benzodiazepines (Valium, diazepam) enhance GABA → sedation and anti-anxiety effects - Acetylcholine (ACh) — used at neuromuscular junctions (nerve-muscle synapses) and in the parasympathetic nervous system. Blocked by organophosphate pesticides and nerve agents - Dopamine — involved in reward, movement, and motivation. Depleted in Parkinson's disease; excess activity linked to schizophrenia - Serotonin — mood regulation. Low serotonin linked to depression; SSRIs (e.g. fluoxetine) block serotonin reuptake → more serotonin available - Noradrenaline (norepinephrine) — sympathetic nervous system; also involved in mood and attention Drugs that target synapses: Almost every drug that affects the brain or nervous system works by modifying synaptic transmission — increasing or decreasing neurotransmitter availability, mimicking neurotransmitters, or blocking receptors. Understanding synaptic physiology is therefore essential for understanding pharmacology.

A reflex is an automatic, involuntary response to a stimulus — processed entirely within the spinal cord, without waiting for input from the brain. Reflexes are fast because the neural circuit is short. The reflex arc — five components: 1. Receptor — detects the stimulus (e.g. stretch receptor in muscle tendon, pain receptor in skin) 2. Afferent (sensory) neuron — carries the signal FROM the receptor TO the spinal cord 3. Integration centre — in the spinal cord (for simple reflexes); synapses here process the signal 4. Efferent (motor) neuron — carries the signal FROM the spinal cord TO the effector 5. Effector — muscle or gland that carries out the response The knee-jerk reflex (patellar reflex): Doctor taps the patellar tendon → stretch receptor in quadriceps muscle is stretched → afferent neuron fires → synapse in spinal cord → motor neuron fires → quadriceps contracts → knee extends (kicks forward). The brain receives a copy of this information but is not involved in the response — it happens before you even feel the tap. Why doctors test reflexes: Reflexes provide instant information about the integrity of specific spinal cord levels and peripheral nerves: - Absent reflex → problem with either the afferent or efferent nerve (or muscle) - Exaggerated reflex → problem with the descending inhibitory pathways from the brain (upper motor neuron lesion, e.g. stroke). The brain normally dampens reflex responses; without this inhibition, reflexes become hyperactive. The withdrawal reflex: Touch something hot → pain receptors fire → signals reach the spinal cord → motor neurons contract the flexor muscles (pulling the limb away) AND simultaneously inhibit the extensor muscles → you withdraw before you've consciously processed the pain. The brain learns about the pain afterwards.

The autonomic nervous system (ANS) controls all the body's involuntary functions — heart rate, blood pressure, digestion, glandular secretions, pupil size, and more. It works in two opposing modes: Sympathetic nervous system — "fight or flight": Activated by stress, exercise, fear, or threat. Prepares the body for physical action: - Heart rate and force ↑ (more blood to muscles) - Arterioles in muscles dilate; in skin and gut constrict (redirect blood) - Bronchioles dilate (more air in) - Pupils dilate (better vision) - Liver releases glucose (energy) - Digestion ↓ (not a priority right now) - Adrenal medulla releases adrenaline (epinephrine) into bloodstream, amplifying all these effects body-wide Parasympathetic nervous system — "rest and digest": Dominant at rest, after meals, during relaxation. Conserves energy and promotes digestion: - Heart rate ↓ - Digestion ↑ — increased gastric acid, intestinal motility, salivation - Pupils constrict - Bronchioles mildly constrict - Bladder contracts (promotes urination) Clinical applications: - Beta-blockers (e.g. atenolol, metoprolol) — block sympathetic beta receptors → lower heart rate and blood pressure. Used for: hypertension, heart failure, angina, arrhythmias - Atropine — blocks parasympathetic (muscarinic) receptors → heart rate increases (used in bradycardia — abnormally slow heart rate) → also dilates pupils (used in eye exams) - Adrenaline (epinephrine) injection — massively activates sympathetic receptors → used in anaphylaxis (severe allergic reaction) to reverse bronchospasm and low blood pressure - Autonomic neuropathy (nerve damage, often from diabetes) → loss of normal heart rate variability, postural hypotension, impaired sweating, erectile dysfunction, gastroparesis (delayed stomach emptying)