7.1 Neurophysiology

Why neurophysiology is a scored Physiology topic

Physiology is 18% of NBCE Part I and is tested in Session 1 with General Anatomy and Spinal Anatomy. Within that domain, neurophysiology is 12%. The official bullets are membrane potentials, action potentials, and synaptic transmission; motor function; sensory function; autonomic function; higher cortical function; and special senses. Named tracts, nuclei, and foramina belong to Spinal Anatomy. This section is mechanisms: which ion, which channel, which transmitter, which reflex sign.

/practice/nbce-part1Practice questions with detailed explanations

Resting membrane potential: Nernst and Goldman–Hodgkin–Katz

A typical neuron sits near −70 mV (inside negative). Skeletal muscle and ventricular myocytes sit closer to −90 mV. That voltage is a permeability-weighted compromise among ionic equilibrium potentials, not the direct voltage of the Na+/K+ pump.

The Nernst equation at 37 °C, using base-10 logs, is:

E_ion (mV) = (61 / z) × log10 ([ion]out / [ion]in)

z is valence (+1 for K+ and Na+, +2 for Ca2+, −1 for Cl−).

Worked K+ example: EK = 61 × log10(4/140) = 61 × log10(0.0286) ≈ 61 × (−1.54) ≈ −94 mV. If extracellular K+ doubles to 8 mM, EK ≈ 61 × log10(8/140) ≈ −76 mV. Hyperkalemia therefore depolarizes resting potential toward threshold, then inactivates voltage-gated Na+ channels and can reduce excitability—the classic trap. Hypokalemia makes EK more negative, so the resting membrane hyperpolarizes and is harder to fire, with cardiac arrhythmias as the clinical cost.

The Goldman–Hodgkin–Katz (GHK) voltage equation weights each Nernst potential by relative permeability:

Vm ≈ 61 × log10 (PK[K]o + PNa[Na]o + PCl[Cl]i) / (PK[K]i + PNa[Na]i + PCl[Cl]o)

At rest PK : PNa is about 20–50 : 1, so Vm hugs EK but remains tens of millivolts more positive (the Na+ leak). During the spike peak, PNa rises hundreds- to thousands-fold and Vm approaches ENa. Cl− terms matter when GABA-A or glycine open Cl− channels.

The Na+/K+ ATPase moves 3 Na+ out and 2 K+ in. It is electrogenic (a few millivolts of direct contribution, often cited as ~3–5 mV) and, more importantly, it maintains the concentration gradients that Nernst potentials require. Acute pump block does not instantly zero RMP; gradients run down over time.

Threshold is typically near −55 mV, where inward INa exceeds outward IK and the cycle becomes regenerative. Subthreshold spread is governed by the length constant (how far current travels) and time constant (how fast voltage changes). Myelin raises effective transmembrane resistance and lowers capacitance, increasing the length constant and speeding conduction.

Extracellular Ca2+ screens Na+ channels. Hypocalcemia lowers threshold (easier firing, tetany). Hypercalcemia raises threshold.

Action-potential phases

A neuronal spike lasts about 1–2 ms. Cardiac muscle is different (plateau of hundreds of milliseconds) and is taught in the next section.

Once threshold is reached at the axon initial segment, the spike is all-or-none. Stimulus intensity is coded by frequency (and recruitment of more axons), not by spike height.

Propagation is local-circuit current: inward Na+ depolarizes the next patch. In myelinated axons, Na+ channels cluster at nodes of Ranvier (internodes often ~0.2–2 mm) → saltatory conduction. Larger diameter and myelin both raise conduction velocity.

Demyelination slows conduction and can block spikes at internodes. Named demyelinating diseases are pathology; the physiology is current leak and failure to bring the next node to threshold.

Synapses and transmitters

Most central synapses are chemical. Terminal depolarization opens P/Q- or N-type voltage-gated Ca2+ channels. Ca2+ binds synaptotagmin; SNARE proteins (syntaxin, SNAP-25, synaptobrevin/VAMP) fuse vesicles. One vesicle is a quantum. Botulinum toxins cleave SNAREs in somatic motor terminals (no acetylcholine release, flaccid paralysis). Tetanus toxin is transported retrogradely into inhibitory interneurons and cleaves synaptobrevin there → disinhibition, spasms, and a locked jaw—not a neuromuscular-junction failure of the extrafusal axon itself.

An excitatory postsynaptic potential (EPSP) depolarizes, usually via AMPA. An inhibitory postsynaptic potential (IPSP) hyperpolarizes or clamps near ECl. Temporal summation stacks PSPs from one terminal; spatial summation adds synapses. The axon initial segment is the decision point.

Short-term facilitation is residual Ca2+; depression is vesicle depletion. Hippocampal long-term potentiation (CA3→CA1) uses NMDA Ca2+ influx to insert more AMPA receptors—the encoding step for declarative memory, not a psychiatry lecture.

At the neuromuscular junction, one motor-axon spike releases enough acetylcholine quanta that the end-plate potential (on the order of 40 mV) far exceeds threshold: a large safety factor. Acetylcholinesterase in the synaptic basal lamina clears transmitter in well under 1 ms. Myasthenia gravis antibodies reduce nicotinic-receptor number, so repeated use eats the safety factor. Lambert–Eaton antibodies against presynaptic P/Q Ca2+ channels cut quantal content; high-frequency use can facilitate as Ca2+ accumulates.

Motor function

Upper motor neurons (UMNs) are cortical and brainstem neurons whose axons descend (corticospinal, corticobulbar, rubrospinal, vestibulospinal, reticulospinal). Lower motor neurons (LMNs) are alpha motor neurons in the ventral horn or cranial-nerve motor nuclei that innervate extrafusal fibers. Gamma motor neurons innervate intrafusal fibers and set spindle sensitivity.

A lumbar disc that compresses a single root is an LMN lesion at that myotome even though the herniation is vertebral. Cord compression above the lumbar enlargement produces UMN signs in the legs. Root versus cord geography is Spinal Anatomy; the sign table is this section.

Muscle spindle. Nuclear bag and chain intrafusal fibers sit in parallel with extrafusal fibers. Group Ia afferents report length and velocity (dynamic). Group II afferents report length (static). Sudden stretch fires Ia → monosynaptic excitation of homonymous alpha motor neurons → stretch (myotatic) reflex. Ia collaterals drive glycinergic interneurons that reciprocally inhibit antagonists.

Gamma loop. Descending drive onto gammas tightens spindles so they remain informative while extrafusal fibers shorten (alpha–gamma coactivation). High gamma bias raises resting tone—the physiologic substrate of a brisk stretch reflex, not a diagnosis of myelopathy.

Golgi tendon organ (GTO). Receptors in series at the musculotendinous junction. Ib afferents fire with tension. The inverse myotatic (autogenic inhibition) path is Ib → inhibitory interneuron → homonymous motor neuron. It redistributes force among motor units and limits excessive tension.

Flexor withdrawal uses A-delta and C nociceptors to excite ipsilateral flexor motor neurons. Crossed extension on the opposite limb preserves stance. Henneman size principle: small, fatigue-resistant motor units (type S, type I fibers) are recruited first; large fatigable units last. Renshaw cells are glycinergic recurrent inhibitors of alpha motor neurons; they stabilize firing rate.

Lateral corticospinal axons (pyramidal decussation in caudal medulla) fractionate distal movement. Vestibulospinal and reticulospinal paths set axial tone. Cerebellum times and corrects errors; basal ganglia select programs (direct versus indirect pathways below).

Sensory function

Transduction converts a stimulus into a graded receptor potential. If that voltage reaches threshold in the afferent, action potentials fire. Labeled lines preserve modality. Intensity is frequency plus recruitment. Phasic receptors fire on change; tonic receptors fire throughout the stimulus.

Dorsal column–medial lemniscus: discriminative touch, vibration, proprioception. Primary afferents ascend ipsilateral fasciculus gracilis (below T6) or cuneatus (above T6), synapse in the medulla, cross as internal arcuate fibers, and travel in the medial lemniscus to VPL, then postcentral gyrus. Face equivalent: principal trigeminal nucleus → trigeminal lemniscus → VPM.

Anterolateral (spinothalamic) system: pain and temperature. Afferents synapse in dorsal horn (laminae I, II, V); second-order axons cross in the anterior white commissure within one or two segments and ascend contralaterally to VPL and to intralaminar thalamus / insula / anterior cingulate for affect. Gate control: large A-beta input can inhibit nociceptive transmission in the dorsal horn via enkephalinergic interneurons; descending raphe and locus coeruleus paths add serotonin and norepinephrine.

Spinocerebellar paths carry unconscious proprioception (dorsal tract uncrossed via inferior cerebellar peduncle; ventral tract double-crossed via superior peduncle).

Two-point discrimination is finest on finger pad and tongue: high receptor density, small receptive fields, large cortical territory—the homunculus as a coding fact, not a drawing exercise.

Autonomic function

A two-neuron peripheral chain. Anatomy of the chain and splanchnic nerves is in /study-guides/nbce-part1/spinal-anatomy-neural/pns-ans-anatomy; transmitters and receptors are tested here.

α1 (Gq): vasoconstriction, pupillary dilator, internal urethral sphincter. α2 (Gi): presynaptic brake on norepinephrine release. β1 (Gs): increase heart rate, atrioventricular conduction, and contractility. β2 (Gs): bronchodilation, dilation of skeletal-muscle arterioles, glycogenolysis. M2: slow the sinus node and atrioventricular node. M3: glands, gut motility, detrusor, pupillary sphincter, ciliary muscle for accommodation.

Baroreflex wiring is expanded under cardiovascular physiology: high mean pressure increases carotid (CN IX) and aortic (CN X) firing, which increases nucleus-tractus-solitarius output, raises vagal tone, and lowers rostral-ventrolateral-medulla sympathetic outflow.

Pupil. Parasympathetic (Edinger–Westphal → CN III → ciliary ganglion → M3 sphincter) constricts. Sympathetic (T1 intermediolateral column → superior cervical ganglion → dilator) dilates. Loss of the sympathetic limb is Horner physiology: miosis, ptosis, anhidrosis—three-neuron chain, not a Part II workup.

Higher cortical function

Primary cortices map one modality (S1, M1, A1, V1). Unimodal association cortex elaborates that map. Heteromodal regions (prefrontal, parieto-temporo-occipital) bind maps.

Language, typically left hemisphere: Broca (inferior frontal, Brodmann 44/45) supports speech production and grammar; Wernicke (posterior superior temporal, area 22) supports comprehension; arcuate fasciculus links them. A stem that spares fluency and comprehension but wrecks repetition is asking for that link.

Prefrontal cortex: working memory (dorsolateral) and value/inhibition (orbitofrontal). Right-dominant parietal cortex supports contralateral spatial attention.

Declarative memory encoding requires hippocampus and adjacent medial temporal cortex; long-term stores are neocortical. Amygdala attaches fear valence. Cerebellum and basal ganglia support procedural skill.

Basal ganglia. Direct pathway: cortex → striatum (D1) → inhibit GPi/SNr → disinhibit thalamus → facilitate movement. Indirect pathway: striatum (D2) → inhibit GPe → disinhibit subthalamic nucleus → excite GPi → increase thalamic inhibition → suppress movement. Nigrostriatal dopamine promotes movement (helps direct, brakes indirect). Loss of that dopamine slows movement—the mechanism is fair game even though disease lists live in pathology.

EEG bands (teaching ranges): delta <4 Hz (deep NREM), theta 4–7 Hz, alpha 8–13 Hz (eyes-closed occipital), beta >13 Hz (activated cortex). REM sleep has a wake-like EEG, skeletal atonia (glycine/GABA onto spinal motor neurons), and ponto-geniculo-occipital waves.

Special-sense physiology

Globe layers and pathways are in /study-guides/nbce-part1/spinal-anatomy-neural/special-senses. Transduction is tested here.

Vision. Photoreceptors are depolarized in the dark (about −40 mV) by a cGMP-gated Na+/Ca2+ dark current. Photon absorption isomerizes 11-cis-retinal to all-trans. Rhodopsin (rods) or cone opsins activate transducin (Gt) → cGMP phosphodiesterase → cGMP falls → channels close → hyperpolarization. Glutamate release onto bipolar cells therefore falls. ON bipolar cells depolarize when glutamate drops (sign-inverting, mGluR6). OFF bipolar cells hyperpolarize (sign-conserving ionotropic glutamate receptors). Ganglion cells fire the only retinal action potentials that leave the eye. Horizontal-cell lateral inhibition builds center-surround contrast. Rods: high sensitivity, saturation in daylight, high convergence. Cones: S/M/L opsins, high acuity at the fovea.

Audition. Endolymph in scala media is high-K+; endocochlear potential is about +80 mV (stria vascularis). Inner-hair-cell tip links open mechanotransduction channels so K+ enters from endolymph → depolarization → Ca2+ → glutamate onto spiral-ganglion afferents (CN VIII). Place code: high frequency at the stiff cochlear base, low frequency at the floppy apex. Outer hair cells amplify via prestin.

Vestibular. Semicircular canals encode angular acceleration (endolymph lags and deflects the cupula). Utricle and saccule encode linear acceleration and head tilt (otoconia load the macula). Push-pull canal pairs and the vestibulo-ocular reflex (medial longitudinal fasciculus) stabilize gaze.

Olfaction. Odorant → Golf → adenylate cyclase → cAMP → cyclic-nucleotide-gated cation channels. CN I axons are C fibers, one receptor type per glomerulus. This is the sensory path that need not relay in thalamus before reaching piriform cortex.

Gustation. Salt: ENaC Na+ influx. Sour: proton influx (OTOP1). Sweet and umami: T1R GPCRs. Bitter: T2R GPCRs. ATP is a key transmitter from taste cells onto afferents of CN VII, IX, and X.