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Complete CNS & Physiology Study Guide

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TOPIC 1: CNS STRUCTURE & FUNCTION

Brain Stem (Medulla, Pons, Midbrain)

• Medulla: Controls respiration, heart rate, blood pressure (vasomotor center), vomiting, swallowing. Cranial nerves IX, X, XI, XII. Contains the inferior olive (source of climbing fibers to cerebellum).
• Pons: Relay for cerebellar signals (pontocerebellar pathway via pontine nuclei). Cranial nerves V, VI, VII, VIII. Pneumotaxic and apneustic centers for respiration.
• Midbrain: Superior/inferior colliculi (visual and auditory reflexes), substantia nigra (dopamine), red nucleus (motor coordination). Cranial nerves III, IV.
• Reticular formation: Runs through all levels; controls arousal/consciousness (ascending reticular activating system - ARAS).

Diencephalon

Cerebral Hemispheres

• Frontal: Primary motor cortex (precentral gyrus), prefrontal (personality, planning, working memory), Broca's area (speech production, dominant hemisphere)
• Parietal: Primary somatosensory cortex (postcentral gyrus), spatial awareness, reading (angular gyrus)
• Temporal: Primary auditory cortex, Wernicke's area (speech comprehension), memory (hippocampus)
• Occipital: Primary visual cortex

Spinal Cord

• Gray matter: H-shaped; dorsal horns (sensory neurons), ventral horns (motor neurons - alpha and gamma motoneurons), lateral horns (autonomic preganglionic neurons at T1-L2 sympathetic, S2-S4 parasympathetic)
• White matter: Ascending and descending tracts

Major Spinal Tracts

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TOPIC 2: CNS LESIONS - UMN vs LMN vs Cerebellar vs Basal Ganglia vs Thalamus

Golden Rule: Know UMN vs LMN First - Everything Else Follows

Spinal Cord Lesion Patterns

• Acute: Spinal shock - flaccid paralysis, areflexia, loss of sensation, urinary retention BELOW the level
• Chronic (weeks): UMN signs below the level, autonomic dysreflexia

• Ipsilateral: UMN signs + loss of fine touch/vibration/proprioception (dorsal columns) BELOW lesion
• Contralateral: Loss of pain and temperature (spinothalamic) BELOW lesion (crosses 1-2 segments above)
• AT the level: LMN signs ipsilaterally (destruction of anterior horn cells at that level)

• Spinothalamic fibers cross in the anterior commissure → bilateral loss of pain & temperature at the level of the lesion ("cape" distribution across shoulders/arms)
• Dorsal columns and corticospinal tracts initially spared
• Anterior horn involvement at the level → LMN weakness at that level

• LMN signs: flaccid paralysis, areflexia, saddle anesthesia, sphincter dysfunction (incontinence or retention)

Cerebellar Lesions

• Vestibulocerebellum lesion: balance problems, nystagmus
• Spinocerebellum lesion: truncal and limb ataxia
• Pontocerebellum lesion: difficulty planning/initiating smooth movements

Basal Ganglia Lesions

Thalamic Lesions

• Unilateral thalamic infarct: Contralateral hemisensory loss (all modalities - because thalamus relays ALL sensory input)
• Thalamic pain syndrome (Dejerine-Roussy): Contralateral burning/aching pain after thalamic infarct
• Bilateral medial thalamic lesion: Severe amnesia (as in Korsakoff syndrome, where mamillothalamic tract damage affects anterior nuclei)

Hypothalamic Lesions

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TOPIC 3: HORMONES - SITE, FUNCTION, REGULATION

Master Framework

Hypothalamic-Pituitary Axis

Thyroid

• Made: Thyroid follicular cells (T3/T4); parafollicular C-cells (calcitonin)
• T3 is active form (T4 is prohormone, converted peripherally by deiodinase)
• Synthesis: TSH → ↑ iodide uptake → thyroid peroxidase (TPO) oxidizes iodide → iodination of tyrosines on thyroglobulin → MIT, DIT → T3 (1 MIT + 1 DIT), T4 (2 DIT)
• Transport: Mostly bound to TBG (thyroid-binding globulin); free fraction is active
• Effects: ↑ BMR, ↑ O2 consumption, ↑ thermogenesis, stimulates synthesis of Na+/K+-ATPase, ↑ cardiac output, necessary for normal growth/development, CNS maturation in fetus

Adrenal Cortex (Zones & Hormones)

Adrenal Medulla

• Epinephrine (80%) and Norepinephrine (20%)
• Secreted from chromaffin cells (modified sympathetic ganglionic neurons) in response to sympathetic activation
• Both are catecholamines (tyrosine → DOPA → dopamine → NE → E)
• Epinephrine: β1 (↑ HR, ↑ contractility), β2 (bronchodilation, vasodilation in muscle, ↓ peripheral resistance overall), α1 (vasoconstriction skin/viscera), metabolic (↑ glycogenolysis, ↑ gluconeogenesis, ↑ lipolysis)
• Norepinephrine: Mainly α1 and β1; causes greater vasoconstriction (↑ peripheral resistance)

Pancreatic Hormones

PTH, Calcitonin, Vitamin D (Calcium Regulation)

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TOPIC 4: NEUROMUSCULAR JUNCTION & EXCITATION-CONTRACTION COUPLING

Neuromuscular Junction (NMJ)

1. Action potential travels down motoneuron to presynaptic terminal
2. Depolarization opens voltage-gated Ca2+ channels in presynaptic terminal membrane → Ca2+ flows in down its electrochemical gradient
3. Ca2+ triggers exocytosis of ACh from synaptic vesicles (quantal release - each vesicle = 1 quantum). ACh is synthesized from acetyl-CoA + choline by choline acetyltransferase and stored in vesicles with ATP
4. ACh diffuses across synaptic cleft to motor end plate; binds nicotinic ACh receptors (ligand-gated Na+/K+ channel) on α subunits
5. Na+ influx > K+ efflux → motor end plate depolarizes to ~-50 mV (end plate potential, EPP). Each vesicle produces a miniature EPP (MEPP) of ~0.4 mV. Need ~100 quanta to reach EPP. EPP is NOT an action potential - it is a graded local depolarization
6. EPP spreads by local currents to adjacent muscle membrane → depolarizes to threshold → muscle action potential fires and propagates along sarcolemma
7. ACh is degraded by acetylcholinesterase (AChE) in synaptic cleft → acetate + choline; choline is recycled into presynaptic terminal via Na+-choline cotransporter

Extrapolating to CNS Synapses

• ACh → any neurotransmitter (glutamate, GABA, dopamine, serotonin, norepinephrine, glycine)
• Nicotinic receptor → AMPA, NMDA, GABA-A, etc. (each is a ligand-gated ion channel)
• EPP → EPSP (excitatory post-synaptic potential) or IPSP (inhibitory)
• No AChE → reuptake transporters, MAO, COMT for catecholamines

• Glutamate (AMPA/NMDA): main excitatory CNS NT
• GABA: main inhibitory CNS NT (hyperpolarizes via Cl- influx); benzodiazepines and barbiturates potentiate GABA-A
• Glycine: inhibitory (spinal cord and brain stem)
• Dopamine: basal ganglia (D1/D2), limbic system; depleted in Parkinson's
• Serotonin (5-HT): mood, sleep, appetite; SSRIs block reuptake
• Norepinephrine: ANS, arousal; locus coeruleus

Excitation-Contraction Coupling in Skeletal Muscle

1. Muscle action potential propagates down T-tubules (transverse tubules = invaginations of sarcolemma that carry depolarization into the muscle interior)
2. Depolarization causes conformational change in dihydropyridine receptors (DHPR) in T-tubule membrane (these are L-type voltage-gated Ca2+ channels but act as voltage sensors in skeletal muscle - Ca2+ influx NOT required here)
3. DHPR physically opens ryanodine receptors (RyR1) on the adjacent sarcoplasmic reticulum (SR) terminal cisternae → Ca2+ floods out of SR into cytoplasm (from <10-7 M to ~10-6 M)
4. Ca2+ binds troponin C on thin filaments → conformational change in troponin complex (troponin C, I, T) → tropomyosin moves away from myosin-binding sites on actin
5. Cross-bridge cycling begins: myosin heads bind actin, hydrolyze ATP, perform power stroke, then detach. Cycle repeats as long as Ca2+ is elevated
6. Relaxation: Ca2+ pumped back into SR by SERCA (sarcoplasmic-endoplasmic reticulum Ca2+-ATPase); tropomyosin blocks actin-myosin binding again

Properties of Muscle

• Twitch: Single contraction-relaxation cycle from a single action potential
• Summation: Rapid repetitive stimuli → twitches add together (mechanical summation) before the muscle fully relaxes
• Tetanus: Stimulation so rapid that twitches fully fuse → smooth sustained maximum tension
• Length-tension relationship: Maximum tension at optimal sarcomere length (~2.0-2.2 μm) where maximum cross-bridge overlap occurs
• Force-velocity relationship: Faster shortening velocity = less force (inverse relationship for concentric contractions)
• Fatigue: Due to Pi accumulation, lactic acid (at high intensity), glycogen depletion, ATP depletion

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TOPIC 5: CLASSIFICATION & PROPERTIES OF NEURONS

Classification by Function

Classification by Morphology (number of processes)

Classification by Axon Diameter and Myelination (Erlanger-Gasser)

Structural Components of a Neuron

• Cell body (soma/perikaryon): Contains nucleus (large, euchromatic, prominent nucleolus), Nissl bodies (rough ER + free ribosomes = the protein synthesis machinery), Golgi apparatus, mitochondria. NO Nissl bodies in axon hillock or axon.
• Dendrites: Multiple; receive synaptic input; contain Nissl bodies; increase receptive surface area via spines
• Axon hillock: Site of action potential initiation (highest density of voltage-gated Na+ channels)
• Axon: Single process; conducts APs away from cell body; covered by myelin (oligodendrocytes in CNS, Schwann cells in PNS)
• Myelin: Increases conduction velocity by saltatory conduction (AP jumps between nodes of Ranvier)
• Synaptic terminals: Contain synaptic vesicles; release neurotransmitter by exocytosis

Properties of Neurons (Action Potentials)

1. Resting (-70 mV): membrane polarized
2. Depolarization: Stimulus reaches threshold (~-55 mV) → voltage-gated Na+ channels open → Na+ rushes in → rapid depolarization to +30 mV (overshoot)
3. Repolarization: Na+ channels inactivate (h gate closes) → voltage-gated K+ channels open → K+ flows out → membrane returns toward -70 mV
4. Afterhyperpolarization (undershoot): K+ channels remain open briefly → membrane temporarily more negative than resting → hyperpolarization
5. Recovery: K+ channels close; Na+/K+ pump restores ion gradients

• All-or-nothing: AP is always the same amplitude once threshold is reached; graded stimuli are encoded as frequency of APs, not amplitude
• Threshold: ~15 mV depolarization above resting potential
• Absolute refractory period: Na+ channels are inactivated; no AP can be generated (corresponds to upstroke and peak of AP). Limits maximum firing frequency.
• Relative refractory period: Na+ channels recovering; AP can be generated but requires stronger-than-normal stimulus. Corresponds to afterhyperpolarization.
• Accommodation: If a stimulus is applied very slowly, Na+ channels inactivate gradually and AP may not fire even when threshold is reached (used by local anesthetics - they work better on rapidly firing neurons)
• Saltatory conduction: In myelinated fibers, depolarization jumps from one node of Ranvier to the next → faster conduction, less energy used
• Conduction velocity: Proportional to axon diameter and degree of myelination (Aα fastest; C fibers slowest)

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INTEGRATED CLINICAL REASONING TABLE

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CNS & Physiology - Quick Study Notes

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1. CNS STRUCTURE & FUNCTION

Brain Parts - What They Do

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2. SPINAL CORD TRACTS (Just 3 to Know)

DORSAL COLUMNS       → Fine touch, vibration, proprioception
                       Crosses at MEDULLA (ipsilateral ascent)

SPINOTHALAMIC        → Pain & temperature
                       Crosses at SPINAL CORD (1-2 segments above entry)

CORTICOSPINAL        → Voluntary movement
                       Crosses at MEDULLA (pyramidal decussation)

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3. UMN vs LMN LESIONS

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4. LESION PATTERNS

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5. CEREBELLAR vs BASAL GANGLIA

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6. HORMONES (One Table per Gland)

Hypothalamus → Anterior Pituitary → Target

CRH → ACTH → CORTISOL (adrenal)
TRH → TSH  → T3/T4 (thyroid)
GnRH → LH/FSH → Estrogen/Testosterone (gonads)
GHRH → GH → IGF-1 (liver/all tissues)
Dopamine → INHIBITS Prolactin

Posterior Pituitary (made in HYPOTHALAMUS, stored in posterior pituitary)

Adrenal Cortex - "GFR = Salt, Sugar, Sex"

Quick Hyper/Hypo Patterns

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7. NEUROMUSCULAR JUNCTION (NMJ)

AP arrives → Ca²⁺ enters presynaptic terminal
→ ACh released (exocytosis, quantal)
→ ACh binds nicotinic receptor (motor end plate)
→ Na⁺ in / K⁺ out → End Plate Potential (EPP)
→ EPP spreads → muscle AP fires
→ AChE breaks down ACh → choline recycled

• Myasthenia Gravis = antibodies vs. post-synaptic receptor → fatigable weakness, worse with use, ptosis
• Lambert-Eaton = antibodies vs. pre-synaptic Ca²⁺ channel → proximal weakness, improves with repeated use

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8. EXCITATION-CONTRACTION COUPLING

Skeletal Muscle

AP → T-tubule depolarization
→ DHPR (voltage sensor) opens RyR1 on SR
→ Ca²⁺ released from SR
→ Ca²⁺ binds Troponin C
→ Tropomyosin moves → actin exposed
→ Myosin binds actin → cross-bridge cycling → CONTRACTION
→ Relaxation: SERCA pumps Ca²⁺ back into SR

Smooth Muscle (different!)

Ca²⁺ enters from outside (voltage-gated channels)
→ Ca²⁺ binds CALMODULIN (no troponin!)
→ Activates MLCK → phosphorylates myosin
→ Cross-bridge cycling → contraction

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9. NEURON CLASSIFICATION

By Function

• Sensory = body to CNS
• Motor = CNS to muscle/gland
• Interneuron = CNS to CNS (99.9% of all neurons!)

By Shape

• Multipolar = 1 axon + many dendrites (most neurons, motor neurons)
• Bipolar = 1 axon + 1 dendrite (retina, ear)
• Pseudounipolar = single process splitting in 2 (sensory/dorsal root ganglion)

By Fiber Speed (A→B→C = fast to slow)

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10. ACTION POTENTIAL (Properties)

Rest (-70mV) → Threshold (-55mV) → Na⁺ in (depolarize) → +30mV
→ Na⁺ channels inactivate → K⁺ out (repolarize) → -70mV
→ Afterhyperpolarization → return to rest

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MASTER CHEAT SHEET

TREMOR:     Moving = Cerebellum    |    Rest = Parkinson's
WEAKNESS:   Stiff+Babinski = UMN  |    Floppy+Fasciculations = LMN
SENSATION:  Dorsal column = touch/vibration (ipsilateral first)
            Spinothalamic = pain/temp (contralateral)
NMJ:        Pre-synaptic problem → Lambert-Eaton
            Post-synaptic problem → Myasthenia Gravis
MUSCLE:     Skeletal = Troponin C  |  Smooth = Calmodulin
HORMONES:   Know the axis → know the feedback → derive all syndromes