Nervous System

Core Explanation

Neuron Structure

The neuron is the functional unit of the nervous system, specialized for rapid electrical and chemical signaling:

• Soma (cell body): Contains the nucleus and most organelles; integrates incoming signals.
• Dendrites: Branched extensions that receive signals from other neurons or sensory receptors.
• Axon: A single, long extension that conducts action potentials away from the soma toward target cells. May be myelinated for faster conduction.
• Axon terminal (synaptic bouton): Swelling at the end of the axon; contains synaptic vesicles filled with neurotransmitter.

Myelin sheath: Produced by Schwann cells (PNS) or oligodendrocytes (CNS), myelin wraps around axons in segments separated by nodes of Ranvier. Myelin insulates the axon and dramatically increases conduction velocity via saltatory conduction — action potentials "jump" from node to node rather than propagating continuously.

The Resting Membrane Potential

All cells have a voltage difference across their plasma membrane, but neurons are specialized to rapidly change this potential. The resting membrane potential is typically −60 to −70 mV (inside negative relative to outside) and is established by:

1. Na⁺/K⁺-ATPase: Pumps 3 Na⁺ out and 2 K⁺ in per ATP, establishing concentration gradients (high Na⁺ outside, high K⁺ inside). Contributes ~5–10 mV directly.
2. K⁺ leak channels: The membrane is far more permeable to K⁺ than Na⁺ at rest. K⁺ diffuses out down its concentration gradient, leaving behind negative ions (proteins, organic anions) that cannot cross the membrane → net negative interior. The equilibrium potential for K⁺ (EK ≈ −90 mV) is the primary determinant of resting potential.
3. The resting potential is a steady state, not equilibrium — Na⁺ constantly leaks in, K⁺ constantly leaks out, and the pump continuously corrects the gradients.

The Action Potential

An action potential is a rapid, transient reversal of membrane potential that propagates along the axon without decay. It is an all-or-none event — once threshold is reached, a full action potential fires.

Phases:

1. Resting state: Voltage-gated Na⁺ and K⁺ channels are closed. Membrane at ~−70 mV.
2. Depolarization: A stimulus opens some voltage-gated Na⁺ channels. If threshold (~−55 mV) is reached, a positive feedback loop activates many more Na⁺ channels → massive Na⁺ influx → membrane potential shoots toward ENa (+60 mV).
3. Repolarization: Na⁺ channels inactivate (different from closing); voltage-gated K⁺ channels open (delayed) → K⁺ efflux → membrane potential falls back toward rest.
4. Hyperpolarization (undershoot): K⁺ channels are slow to close → membrane briefly becomes more negative than resting potential.
5. Return to rest: K⁺ channels close; Na⁺/K⁺ pump and leak channels restore resting gradients.

Refractory periods:

• Absolute refractory period: No stimulus, regardless of strength, can trigger another action potential (Na⁺ channels are inactivated).
• Relative refractory period: A stronger-than-normal stimulus can trigger an action potential (some Na⁺ channels recovered; membrane hyperpolarized).

Refractory periods ensure unidirectional propagation and limit the maximum firing rate.

Propagation: In unmyelinated axons, action potentials propagate continuously — depolarization of one region triggers Na⁺ channel opening in the adjacent region. In myelinated axons, saltatory conduction allows the action potential to jump between nodes of Ranvier, where Na⁺ channels are concentrated. This is faster (up to ~150 m/s vs ~2 m/s) and more energy-efficient.

Synaptic Transmission

When the action potential reaches the axon terminal, the electrical signal is converted to a chemical signal at the synapse:

1. Action potential depolarizes the presynaptic terminal.
2. Voltage-gated Ca²⁺ channels open; Ca²⁺ influx triggers synaptic vesicle fusion with the membrane (SNARE protein-mediated exocytosis).
3. Neurotransmitter is released into the synaptic cleft (~20–40 nm wide).
4. Neurotransmitter diffuses across and binds to receptors on the postsynaptic membrane.
5. Ion channels open or close → change in postsynaptic membrane potential.

Postsynaptic potentials are graded (not all-or-none):

• EPSP (excitatory postsynaptic potential): Depolarization (typically Na⁺ influx); brings membrane closer to threshold.
• IPSP (inhibitory postsynaptic potential): Hyperpolarization (typically Cl⁻ influx or K⁺ efflux); moves membrane away from threshold.

A single EPSP is rarely sufficient to reach threshold. Instead, the postsynaptic neuron integrates hundreds to thousands of inputs — summing EPSPs and IPSPs in both space (spatial summation) and time (temporal summation). Only if the net depolarization at the axon hillock reaches threshold does the postsynaptic neuron fire its own action potential.

Termination of the signal:

• Neurotransmitter is removed from the cleft by enzymatic degradation (e.g., acetylcholinesterase breaks down ACh), reuptake into the presynaptic terminal (e.g., serotonin, dopamine), or diffusion.

CNS and PNS

The nervous system is divided into:

Central Nervous System (CNS): Brain and spinal cord. Integration and processing.

Peripheral Nervous System (PNS): Nerves and ganglia outside the CNS.

• Sensory (afferent) division: Carries signals FROM sensory receptors TO the CNS.
• Motor (efferent) division: Carries signals FROM the CNS TO effectors (muscles, glands).
  • Somatic nervous system: Voluntary control of skeletal muscles (single motor neuron from CNS to muscle; ACh as neurotransmitter).
  • Autonomic nervous system (ANS): Involuntary control of cardiac muscle, smooth muscle, and glands. Two-neuron chain (preganglionic → ganglion → postganglionic).
    • Sympathetic: "Fight or flight" — increases heart rate, dilates airways, inhibits digestion, mobilizes glucose. Preganglionic neurons in thoracic/lumbar spinal cord; short preganglionic, long postganglionic; neurotransmitter: norepinephrine at target (ACh at ganglia).
    • Parasympathetic: "Rest and digest" — decreases heart rate, stimulates digestion, constricts pupils. Preganglionic neurons in brainstem/sacral spinal cord; long preganglionic, short postganglionic; neurotransmitter: ACh at both ganglia and target.

Sensory Systems

Sensory transduction is the conversion of a physical stimulus into an electrical signal:

Vision:

• Light enters through cornea → lens focuses → projected onto retina.
• Photoreceptors: Rods (dim light, grayscale, high sensitivity; contain rhodopsin) and cones (bright light, color vision, high acuity; three types for red/green/blue).
• Photon absorption → retinal isomerization → activates transducin (G protein) → phosphodiesterase activation → cGMP breakdown → Na⁺ channels close → hyperpolarization → decreased glutamate release → signal to bipolar cells → ganglion cells → optic nerve → brain.
• Photoreceptors are unusual: They are depolarized and releasing neurotransmitter in the DARK. Light causes hyperpolarization and REDUCES neurotransmitter release — fundamentally different from most sensory cells.

Hearing:

• Sound waves → tympanic membrane vibrates → ossicles (malleus, incus, stapes) amplify → oval window → fluid waves in cochlea.
• Organ of Corti in the cochlear duct contains hair cells on the basilar membrane.
• Fluid movement bends stereocilia → mechanically-gated ion channels open → K⁺ influx (unusual — endolymph is high K⁺) → depolarization → Ca²⁺ influx → neurotransmitter release → auditory nerve.
• Frequency discrimination: high frequencies displace the basilar membrane near the base (stiff, narrow); low frequencies displace near the apex (wide, flexible) — tonotopic mapping.