Comprehensive Neuroanatomy, Sensory Systems, and Motor Control Study Guide

Central Nervous System (CNS) vs. Peripheral Nervous System (PNS)

The CNS comprises the brain and spinal cord enclosed in bone and suspended in CSF, serving as the primary integrative center. The PNS consists of all neural tissue outside the cranium and vertebral canal, divided into cranial nerves, spinal nerves, and the autonomic nervous system.

Spinal Roots: Functional Segregation

Dorsal roots carry afferent sensory signals into the dorsal horn, with cell bodies located in the dorsal root ganglion (DRG). Ventral roots carry efferent motor signals away from lower motor neurons in the ventral horn to skeletal muscle effectors.

Autonomic Neurotransmitters

The sympathetic division utilizes acetylcholine (ACh) in preganglionic fibers and norepinephrine (NE) in postganglionic fibers (fight-or-flight). The parasympathetic division uses ACh at both pre- and postganglionic synapses (rest-and-digest).

Glymphatic System

A convective waste-clearance system driving CSF bulk inflow through periarterial spaces via astrocytic Aquaporin-4 ($\text{AQP4}$) water channels. Interstitial space volume increases by $60\%$ during slow-wave NREM sleep, boosting metabolic waste clearance ($\text{A}\beta$, tau) over tenfold.

The Cooking Hypothesis

Proposed by Dr. Suzana Herculano-Houzel; human brains contain $86\text{ billion}$ neurons ($16\text{ billion}$ in the cerebral cortex) at an energetically expensive metabolic cost of $6\,\text{kCal}$ per billion neurons daily. Thermal cooking expanded caloric bioavailability to overcome metabolic constraints on cortical neuron count.

Cortical Layers IV, V, and VI

Layer $\text{IV}$ (internal granular) is the primary thalamocortical recipient layer. Layer $\text{V}$ contains subcortical projection neurons, including giant Betz cells in M1 and von Economo spindle cells in anterior cingulate/frontoinsular cortex. Layer $\text{VI}$ gives rise to corticothalamic feedback projections.

Diffusion Tensor Imaging (DTI)

An MRI-based modality measuring the fractional anisotropy of water diffusion along white matter axonal tracts; useful for detecting early microstructural connectivity alterations in infants at risk for autism before behavioral symptoms manifest.

Salty and Sour Taste Transduction

Salty: Inward $Na^+$ influx through constitutively open Epithelial Sodium Channels ($\text{ENaC}$) depolarizes the taste cell. Sour: Protons ($H^+$) pass into Type III taste cells via Otopetrin-1 ($\text{OTOP1}$) channels, causing intracellular acidification and potassium channel closure to evoke depolarization.

Sweet, Umami, and Bitter Taste Transduction

G-protein-coupled receptor (GPCR) activation ($\text{TAS1R2}+\text{TAS1R3}$ for sweet, $\text{TAS1R1}+\text{TAS1R3}$ for umami, $\text{TAS2Rs}$ for bitter) activates $\text{PLC}\beta2$, triggering $\text{IP}_3$-mediated $Ca^{2+}$ release from the ER. Elevated $Ca^{2+}$ opens $\text{TRPM5}$ cation channels to depolarize the cell, releasing non-vesicular ATP through $\text{CALHM1/3}$ channels.

Olfactory Transduction Cascade

Odorant binding to GPCRs activates $\text{G}_{\text{olf}}$ $\rightarrow$ adenylyl cyclase III ($\text{ACIII}$) increases $\text{cAMP}$ $\rightarrow$ cyclic nucleotide-gated ($\text{CNG}$) channels open, causing $Na^+$ and $Ca^{2+}$ influx $\rightarrow$ $Ca^{2+}$-activated $\text{ANO2}$ chloride channels open, causing $Cl^-$ efflux (due to high intracellular chloride maintained by $\text{NKCC1}$) to amplify depolarization.

COVID-19-Induced Anosmia

Caused by SARS-CoV-2 infection and lysis of supporting sustentacular cells expressing $\text{ACE2}$ and $\text{TMPRSS2}$, which impairs olfactory epithelial structural and ciliary support without direct viral infection of olfactory receptor neurons.

Phototransduction Cascade (in Light)

Photon absorption isomerizes 11-cis-retinal to all-trans-retinal in rhodopsin $\rightarrow$ transducin ($\text{G}_t$) activation $\rightarrow$ phosphodiesterase ($\text{PDE}$) activation $\rightarrow$ hydrolysis of $\text{cGMP}$ to $5'\text{-GMP}$ $\rightarrow$ closure of $\text{cGMP}$-gated sodium channels $\rightarrow$ termination of the inward dark current, hyperpolarizing the photoreceptor from $-30\,\text{mV}$ to $-65\,\text{mV}$ and decreasing tonic glutamate release.

ON-Center vs. OFF-Center Bipolar Cells

OFF-center bipolar cells express ionotropic AMPA/kainate receptors and hyperpolarize to light in the center (sign-conserving). ON-center bipolar cells express metabotropic $\text{mGluR6}$ receptors, which invert the signal, causing depolarization when light reduces glutamate release (sign-inverting).

M-Type vs. P-Type Retinal Ganglion Cells

M-type cells ($5\%$ of population) have large receptive fields, transient action potential bursts, fast conduction velocities, and high contrast sensitivity for motion. P-type cells ($90\%$ of population) feature small receptive fields, sustained firing, and color-opponent channels for shape and fine detail.

Visual Pathway Deficits

Transection of an optic nerve causes ipsilateral monocular blindness; lesion of the optic chiasm interrupts decussating nasal fibers, causing bitemporal hemianopsia; transection of an optic tract or optic radiation causes contralateral homonymous hemianopsia.

Dorsal vs. Ventral Extrastriate Streams

The Dorsal Stream ('Where/How') projects to area MT/$V_5$ and parietal cortex to analyze visual motion, spatial awareness, and navigation (damage causes akinetopsia). The Ventral Stream ('What') projects to area $V_4$ and inferior temporal cortex (IT) to process color, shape, and complex object/face identity (damage causes cerebral achromatopsia or prosopagnosia).

Cutaneous Mechanoreceptor Properties

Meissner's corpuscles: small receptive field, rapid adaptation. Merkel's disks: small receptive field, slow adaptation. Pacinian corpuscles: large receptive field, rapid adaptation ($200\text{--}300\,\text{Hz}$ vibration). Ruffini endings: large receptive field, slow adaptation.

Pacinian Corpuscle Mechanical Filtering

The fluid-filled concentric lamellae of the capsule deform transiently in response to mechanical pressure and quickly redistribute the energy, filtering out steady pressures and leaving only rapid dynamic onset/offset oscillations. Decapsulation converts the Pacinian corpuscle into a slowly adapting receptor.

Dorsal Column-Medial Lemniscal (DCML) Pathway

Carries fine touch, vibration, and proprioception: primary $A\beta$ fibers ascend ipsilaterally through the dorsal columns (fasciculus gracilis for lower body, fasciculus cuneatus for upper body) $\rightarrow$ synapse in medullary dorsal column nuclei $\rightarrow$ second-order fibers decussate as internal arcuate fibers $\rightarrow$ ascend medial lemniscus $\rightarrow$ VPL thalamus $\rightarrow$ primary somatosensory cortex ($S_1$).

Dual Nociceptive Afferents ($A\delta$ vs. C Fibers)

$A\delta$ fibers are lightly myelinated with intermediate conduction velocities ($5\text{--}30\,\text{m/s}$) mediating localized, fast, sharp 'first pain'. C fibers are unmyelinated with slow conduction velocities ($0.5\text{--}2\,\text{m/s}$) mediating diffuse, throbbing, dull 'second pain'.

Spinothalamic Pathway

Carries pain and temperature: primary nociceptive afferents enter the dorsal horn substantia gelatinosa $\rightarrow$ synapse on second-order projection neurons that decussate immediately across the anterior white commissure $\rightarrow$ ascend via the contralateral anterolateral funiculus $\rightarrow$ VPL thalamus $\rightarrow$ $S_1$ and insular/anterior cingulate cortices.

Brown-Séquard Syndrome

A hemisection of the spinal cord resulting in ipsilateral loss of fine touch, vibration, and proprioception below the lesion (due to interruption of the uncrossed ascending DCML fibers) and contralateral loss of pain and temperature below the lesion (due to interruption of the crossed spinothalamic tract).

Afferent Gate Control Theory of Pain

Simultaneous non-nociceptive mechanical stimulation ($A\beta$ fibers) excites inhibitory interneurons in the spinal dorsal horn, which presynaptically and postsynaptically inhibit spinothalamic projection neurons, reducing ascending nociceptive transmission.

Henneman's Size Principle

Motor units are systematically recruited in order from smallest to largest threshold: Slow (Type I, fatigue-resistant, low force) units are recruited first, followed by Fast Fatigue-Resistant (Type IIa), and finally Fast Fatigable (Type IIb/x, glycolytic, maximal force) units as force requirements escalate.

Neuromuscular Excitation-Contraction Coupling

ACh binds nicotinic receptors $\rightarrow$ endplate potential triggers sarcolemmal action potential down T-tubules $\rightarrow$ conformational shift in voltage-gated dihydropyridine receptors (DHPR) activates ryanodine receptors (RyR1) $\rightarrow$ $Ca^{2+}$ released from sarcoplasmic reticulum binds Troponin C $\rightarrow$ tropomyosin moves off actin active sites $\rightarrow$ myosin power stroke occurs.

Myotatic (Stretch) vs. Crossed-Extensor Reflex

Myotatic reflex: Monosynaptic excitation of alpha motor neurons via Group Ia muscle spindle afferents following muscle stretch, paired with reciprocal inhibition of antagonist muscles. Crossed-extensor reflex: Polysynaptic reflex where nociceptive input causes ipsilateral limb flexion (withdrawal) and contralateral limb extension to maintain postural equilibrium.

Lateral vs. Ventromedial Descending Motor Pathways

Lateral pathways (corticospinal and rubrospinal tracts) cross at the medullary pyramids and govern voluntary, fractionated distal limb movements. Ventromedial pathways (vestibulospinal, tectospinal, pontine reticulospinal, medullary reticulospinal) descend bilaterally/ipsilaterally to control axial posture, balance, and orienting reflexes.

Basal Ganglia: Direct vs. Indirect Pathway

Direct Pathway ('Go'): Striatal GABAergic neurons inhibit GPi/SNr, disinhibiting the VL thalamus to initiate movement (promoted by dopamine via $D_1$ receptors). Indirect Pathway ('No-Go'): Striatum inhibits GPe $\rightarrow$ disinhibits STN $\rightarrow$ excites GPi $\rightarrow$ increases inhibition on VL thalamus, suppressing unintended movement (inhibited by dopamine via $D_2$ receptors).

Parkinson's Disease Pathophysiology

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta ($\text{SNc}$) and intracellular $\alpha$-synuclein aggregation (Lewy bodies). Loss of striatal dopamine causes overactivation of the STN and GPi, leading to pathological hyperinhibition of the motor thalamus and cardinal symptoms: resting tremor, bradykinesia, rigidity, and postural instability.