Nervous System

Neuron Structure

Neurons are specialized cells designed to receive, integrate, and transmit electrical signals. The cell body (soma) contains the nucleus and most organelles. Dendrites are branched extensions that receive incoming signals from other neurons; their surface is studded with ligand-gated ion channels that open when neurotransmitters bind. The axon is a single, long projection that conducts action potentials away from the soma toward target cells. The axon hillock, where the axon emerges from the soma, is the site of action potential initiation due to its high density of voltage-gated Na⁺ channels. Many axons are wrapped in a myelin sheath formed by Schwann cells (PNS) or oligodendrocytes (CNS); myelin insulates the axon and increases conduction velocity via saltatory conduction. Gaps between myelin segments, called nodes of Ranvier, are densely packed with voltage-gated Na⁺ channels where the action potential is regenerated. Axon terminals (synaptic boutons) contain synaptic vesicles loaded with neurotransmitter, ready for Ca²⁺-triggered exocytosis. Structural proteins in the cytoskeleton (microtubules, neurofilaments) mediate anterograde (kinesin-driven) and retrograde (dynein-driven) axonal transport of organelles and vesicles.

Resting Membrane Potential

All cells maintain an electrical potential difference across the plasma membrane, but neurons exploit it for signaling. The resting membrane potential (RMP) of a typical neuron is approximately −70 mV (inside negative relative to outside). This potential arises from two factors: (1) the unequal distribution of ions across the membrane, maintained by the Na⁺/K⁺ ATPase, which pumps 3 Na⁺ out and 2 K⁺ in per ATP hydrolyzed, and (2) the selective permeability of the resting membrane, which is far more permeable to K⁺ than to Na⁺ due to constitutively open K⁺ leak channels. K⁺ diffuses out of the cell down its concentration gradient, leaving behind impermeant anions (e.g., proteins, phosphate), creating the negative interior. The Nernst equation, Eᵢₒₙ = (RT/zF) ln([ion]ₒᵤₜ/[ion]ᵢₙ), calculates the equilibrium potential for a single ion. The Goldman-Hodgkin-Katz (GHK) equation extends this to multiple ions weighted by their relative permeability: Vₘ = (RT/F) ln( (P_K[K⁺]ₒᵤₜ + P_Na[Na⁺]ₒᵤₜ + P_Cl[Cl⁻]ᵢₙ) / (P_K[K⁺]ᵢₙ + P_Na[Na⁺]ᵢₙ + P_Cl[Cl⁻]ₒᵤₜ) ). Because resting P_K ≫ P_Na, Vₘ sits near E_K (−90 mV) but is slightly depolarized by the small Na⁺ leak. Changes in extracellular K⁺ concentration directly alter RMP; hyperkalemia depolarizes, hypokalemia hyperpolarizes.

Action Potentials

An action potential is a rapid, transient, all-or-nothing reversal of membrane potential that propagates without decrement along the axon. It is triggered when the membrane depolarizes to threshold (approximately −55 mV), opening voltage-gated Na⁺ channels. The action potential has distinct phases. Rising phase: voltage-gated Na⁺ channels open, Na⁺ rushes in, and the membrane rapidly depolarizes toward E_Na (+50 mV). At the peak, Na⁺ channels inactivate (ball-and-chain mechanism) and voltage-gated K⁺ channels, which open more slowly, are now fully open. Falling phase: K⁺ efflux through open K⁺ channels repolarizes the membrane back toward E_K. Undershoot (hyperpolarization): K⁺ channels remain open longer than needed, causing the membrane to transiently overshoot the resting potential before closing. The absolute refractory period (Na⁺ channels inactivated) prevents another action potential regardless of stimulus strength. The relative refractory period (Na⁺ channels recovering from inactivation, K⁺ channels still open) requires a larger-than-normal stimulus. This refractory behavior ensures unidirectional propagation and limits firing frequency. Action potential propagation velocity increases with axon diameter and myelination; the length constant (λ = √(rₘ/rₐ)) describes how far a depolarization spreads passively before decaying.

Synaptic Transmission

Synapses convert the electrical signal of an action potential into a chemical signal and back into an electrical signal in the postsynaptic cell. At the presynaptic terminal, depolarization opens voltage-gated Ca²⁺ channels; the resulting Ca²⁺ influx (driven by a steep electrochemical gradient) triggers SNARE-protein-mediated fusion of synaptic vesicles with the plasma membrane, releasing neurotransmitter into the synaptic cleft via exocytosis. Neurotransmitter diffuses across the ~20 nm cleft and binds to postsynaptic receptors, which fall into two classes: ionotropic receptors (ligand-gated ion channels) produce fast, direct responses by opening and allowing ion flux across the membrane; metabotropic receptors (G-protein-coupled receptors) produce slower, indirect responses via second messenger cascades that can modulate ion channels or gene expression. The postsynaptic potential (PSP) can be excitatory (EPSP, depolarizing toward threshold via Na⁺ or Ca²⁺ influx) or inhibitory (IPSP, hyperpolarizing away from threshold via Cl⁻ influx or K⁺ efflux). Signal termination occurs through neurotransmitter reuptake (transporters), enzymatic degradation (e.g., acetylcholinesterase in the cleft), or diffusion away from the synapse. At the axon hillock, multiple EPSPs and IPSPs are integrated; if the net depolarization reaches threshold, an action potential fires—this is the fundamental computation performed by each neuron.

Neurotransmitters

Neurotransmitters are the chemical messengers of the nervous system, classified by structure and function. Acetylcholine (ACh) is used at the neuromuscular junction (nicotinic receptors, ionotropic/excitatory) and in the autonomic and central nervous systems (muscarinic receptors, metabotropic). The amino acid neurotransmitters include glutamate (the primary excitatory neurotransmitter in the CNS; ionotropic NMDA/AMPA/kainate and metabotropic receptors) and GABA (the primary inhibitory neurotransmitter; GABA_A is ionotropic/Cl⁻ channel, GABA_B is metabotropic). Glycine serves as an inhibitory transmitter primarily in the spinal cord. Biogenic amines (monoamines) derive from amino acids: dopamine (reward, movement, prolactin inhibition), norepinephrine (alertness, sympathetic activation), epinephrine (fight-or-flight), serotonin/5-HT (mood, sleep, appetite), and histamine (wakefulness, gastric acid). Catecholamines (dopamine, norepinephrine, epinephrine) share the synthetic pathway: tyrosine → L-DOPA → dopamine → norepinephrine → epinephrine. Neuropeptides (e.g., substance P, endorphins, oxytocin) are larger, slower-acting modulators. Nitric oxide (NO) is an unconventional gaseous retrograde neurotransmitter that diffuses through membranes. For the MCAT, know each neurotransmitter's primary receptor type (ionotropic vs. metabotropic), major functions, and clinical correlations (e.g., dopamine loss in Parkinson's, ACh loss in Alzheimer's, GABA potentiation by benzodiazepines).

Central and Peripheral Nervous Systems

The nervous system is divided anatomically and functionally. The central nervous system (CNS) comprises the brain and spinal cord. The brain is organized into the forebrain (telencephalon: cerebral cortex, basal ganglia, limbic system; diencephalon: thalamus, hypothalamus), midbrain (mesencephalon: superior and inferior colliculi, substantia nigra, ventral tegmental area), and hindbrain (metencephalon: pons, cerebellum; myelencephalon: medulla oblongata). The spinal cord carries ascending sensory tracts (dorsal columns for fine touch/proprioception, spinothalamic tract for pain/temperature) and descending motor tracts (corticospinal/pyramidal tract for voluntary movement). The peripheral nervous system (PNS) includes all nerves outside the CNS and divides into the somatic nervous system (voluntary control of skeletal muscle via α-motor neurons; acetylcholine at NMJ) and the autonomic nervous system (involuntary control of viscera, smooth muscle, glands). The autonomic nervous system has two antagonistic divisions: sympathetic (fight-or-flight; preganglionic ACh → postganglionic norepinephrine; thoracolumbar origin; short pre, long post; chain ganglia near spinal cord) and parasympathetic (rest-and-digest; ACh at both pre- and postganglionic synapses; craniosacral origin; long pre, short post; ganglia near target organs). The enteric nervous system, a semi-autonomous network in the GI tract, is sometimes considered a third autonomic division.

Reflexes and Sensory Processing

Reflexes are rapid, involuntary, stereotyped responses to stimuli, mediated by neural circuits called reflex arcs that bypass conscious brain processing. The simplest is the monosynaptic stretch reflex (e.g., patellar/knee-jerk reflex): muscle spindle stretch activates Ia sensory afferents that synapse directly onto α-motor neurons in the spinal cord, causing contraction of the same muscle. It also involves a polysynaptic inhibitory interneuron that relaxes the antagonist muscle (reciprocal inhibition). The withdrawal/flexor reflex (e.g., touching a hot stove) involves multiple synapses: nociceptor afferents activate excitatory interneurons to flexor motor neurons (withdrawal) and inhibitory interneurons to extensor motor neurons, plus crossed extensor interneurons to stabilize posture on the opposite limb. Sensory processing begins with transduction at sensory receptors: mechanoreceptors (touch, hearing, proprioception), photoreceptors (vision), chemoreceptors (taste, smell), thermoreceptors (temperature), and nociceptors (pain). Sensory information is encoded by modality (labeled line principle), intensity (firing rate), duration (adaptation: tonic vs. phasic receptors), and location (receptive fields, lateral inhibition for edge enhancement). Somatosensory pathways relay through the thalamus to primary somatosensory cortex in the postcentral gyrus, organized somatotopically (sensory homunculus). Understanding adaptation, two-point discrimination, and receptive field convergence ties directly to P/S sensation and perception passages.

How it works

The nervous system operates on a deceptively simple principle: convert stimulus to electrical signal, propagate it, and convert it back to a response. Ion gradients created by the Na⁺/K⁺ pump act as a charged battery across the membrane. Voltage-gated Na⁺ and K⁺ channels open and close with exquisite timing to generate the action potential waveform. At the synapse, Ca²⁺ serves as the trigger coupling electricity to chemistry—depolarization opens Ca²⁺ channels, and Ca²⁺ drives vesicle fusion. The postsynaptic cell integrates EPSPs and IPSPs through spatial and temporal summation; if net depolarization at the axon hillock crosses threshold, the cycle repeats. The system's diversity comes from receptor subtypes, neurotransmitter identities, and circuit architecture, but the atomic unit—the neuron summing inputs and firing or not firing—is universal. When tackling MCAT passages, trace the flow: stimulus → receptor potential → action potential → neurotransmitter release → postsynaptic potential → integration → output. Identify what ion moves where, what channel mediates it, and whether it depolarizes or hyperpolarizes.

How it works

The nervous system operates on a deceptively simple principle: convert stimulus to electrical signal, propagate it, and convert it back to a response. Ion gradients created by the Na⁺/K⁺ pump act as a charged battery across the membrane. Voltage-gated Na⁺ and K⁺ channels open and close with exquisite timing to generate the action potential waveform. At the synapse, Ca²⁺ serves as the trigger coupling electricity to chemistry—depolarization opens Ca²⁺ channels, and Ca²⁺ drives vesicle fusion. The postsynaptic cell integrates EPSPs and IPSPs through spatial and temporal summation; if net depolarization at the axon hillock crosses threshold, the cycle repeats. The system's diversity comes from receptor subtypes, neurotransmitter identities, and circuit architecture, but the atomic unit—the neuron summing inputs and firing or not firing—is universal. When tackling MCAT passages, trace the flow: stimulus → receptor potential → action potential → neurotransmitter release → postsynaptic potential → integration → output. Identify what ion moves where, what channel mediates it, and whether it depolarizes or hyperpolarizes.

Comparisons

• C/P (Nernst and Goldman equations): Quantitative predictions of membrane potential from ion concentrations. E_ion = (RT/zF) ln([ion]_out/[ion]_in). At 37°C, simplify to E_ion = (61.5/z) log([ion]_out/[ion]_in). GHK for multi-ion permeability.
• C/P (Cable properties): Length constant λ = √(r_m/r_a) and time constant τ = r_m × c_m determine passive spread of depolarization; myelination increases r_m, increasing λ and conduction velocity.
• B/B (Cell biology): SNARE proteins (synaptobrevin, syntaxin, SNAP-25) mediate vesicle fusion; botulinum and tetanus toxins cleave SNAREs to block neurotransmission.
• B/B (Transport): Na⁺/K⁺ ATPase is a primary active transporter; Na⁺/Ca²⁺ exchanger and neurotransmitter reuptake transporters are secondary active transporters.
• P/S (Psychopharmacology): SSRIs block serotonin reuptake; MAOIs inhibit monoamine oxidase; benzodiazepines enhance GABA_A receptor function; antipsychotics block dopamine D2 receptors.
• P/S (Sensation and perception): Weber's law, signal detection theory, and receptor adaptation (tonic vs. phasic) tie directly to sensory processing and psychophysics questions.

Common confusions

• Confusing the Nernst equation (single ion) with the Goldman equation (multiple ions, weighted by permeability). The MCAT may ask which equation to use for a given scenario.
• Forgetting that the Na⁺/K⁺ ATPase is electrogenic—it pumps 3 Na⁺ out and 2 K⁺ in, contributing a small hyperpolarizing current directly, beyond just maintaining gradients.
• Misidentifying the ionic basis of each action potential phase. Rising phase = Na⁺ influx (voltage-gated Na⁺ channels open). Falling phase = K⁺ efflux (voltage-gated K⁺ channels open). The peak = Na⁺ channel inactivation, not opening of K⁺ channels (though they overlap). Undershoot = K⁺ channels remain open after Na⁺ channels have recovered.
• Thinking the absolute refractory period is caused by K⁺ channel opening. It is caused by Na⁺ channel inactivation—during the absolute refractory period, Na⁺ channels cannot reopen regardless of stimulus.
• Mixing up spatial and temporal summation. Temporal = single synapse, rapid successive EPSPs. Spatial = multiple synapses, simultaneous EPSPs. Both summate at the axon hillock.
• Confusing ionotropic and metabotropic receptors. Ionotropic = ligand-gated ion channels = fast EPSP/IPSP directly. Metabotropic = GPCR = slower, second messenger cascades; can modulate ion channels or gene expression.
• Misattributing sympathetic vs. parasympathetic neurotransmitters. Sympathetic postganglionic = norepinephrine (except sweat glands = ACh). Parasympathetic pre- and postganglionic = ACh. Preganglionic for both = ACh (nicotinic).
• Assuming EPSP = Na⁺ always. An EPSP can also result from Ca²⁺ influx or closure of K⁺ channels. An IPSP can result from Cl⁻ influx or K⁺ efflux. The determining factor is whether the membrane potential moves closer to or further from threshold.

Quick review

• Resting potential ≈ −70 mV; maintained by Na⁺/K⁺ ATPase (3 Na⁺ out, 2 K⁺ in) and K⁺ leak channels.
• Nernst: E_ion = (RT/zF) ln(out/in). Goldman: V_m weighted by permeability (P_K, P_Na, P_Cl).
• Action potential phases: Rising (Na⁺ in via VG Na⁺ channels) → Peak (Na⁺ inactivation) → Falling (K⁺ out via VG K⁺ channels) → Undershoot (K⁺ channels still open).
• Absolute refractory: Na⁺ channels inactivated. Relative refractory: Na⁺ recovering, K⁺ still open; need larger stimulus.
• Synaptic transmission: AP → Ca²⁺ influx → SNARE vesicle fusion → exocytosis → transmitter → postsynaptic receptors (ionotropic = fast, metabotropic = slow/GPCR).
• EPSP (depolarizing, toward threshold) vs. IPSP (hyperpolarizing, away from threshold). Spatial summation (multiple synapses) vs. temporal summation (rapid succession, one synapse).
• CNS = brain + spinal cord. PNS = somatic (voluntary, ACh at NMJ) + autonomic (sympathetic = NE, parasympathetic = ACh).
• Myelin: Schwann cells (PNS), oligodendrocytes (CNS). Nodes of Ranvier concentrate Na⁺ channels → saltatory conduction.
• Glutamate = primary excitatory CNS transmitter. GABA = primary inhibitory CNS transmitter (GABA_A = Cl⁻ channel).
• Dopamine pathway: substantia nigra → striatum. Loss in Parkinson's. ACh loss in Alzheimer's.
• Stretch reflex = monosynaptic (Ia afferent → α-motor neuron). Withdrawal reflex = polysynaptic + crossed extensor.
• Sensory receptor types: tonic (slow-adapting, sustained) vs. phasic (fast-adapting, onset/offset). Lateral inhibition sharpens contrast.