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NERVOUS SYSTEM - PHYSIOLOGY: COMPLETE NOTES

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1. ORGANIZATION OF THE NERVOUS SYSTEM

Central Nervous System (CNS)

1. Spinal cord level - Executes stereotyped reflexes (withdrawal, walking movements, visceral reactions). Programmed for specific motor patterns using only spinal cord circuitry.
2. Subcortical (lower brain) level - Includes brainstem, cerebellum, basal ganglia, thalamus, hypothalamus. Controls subconscious vital functions: blood pressure, breathing, balance, emotional patterns, feeding, sexual activity.
3. Cortical (higher brain) level - The cerebral cortex stores information (memory), provides precise control of voluntary movements, and is essential for language, thinking, and cognition.

• Cerebral hemispheres - Cerebral cortex + underlying white matter + deep nuclei (basal ganglia, hippocampus, amygdala). Functions: perception, higher motor control, cognition, memory, emotion.
• Diencephalon - Thalamus + hypothalamus. Thalamus processes sensory and motor relay; hypothalamus regulates temperature, food intake, water balance, pituitary hormones.
• Brainstem (midbrain, pons, medulla) - Controls vital functions; contains cranial nerve nuclei.
• Cerebellum - Coordinates movement, posture, balance.

Peripheral Nervous System (PNS)

• Somatic nervous system - Controls voluntary skeletal muscles; carries somatic sensory information.
• Autonomic nervous system (ANS) - Controls smooth muscle, cardiac muscle, glands. Divided into:
  • Sympathetic ("fight or flight") - thoracolumbar (T1-L2)
  • Parasympathetic ("rest and digest") - craniosacral (CN III, VII, IX, X; S2-S4)
• Enteric nervous system - Semi-autonomous network in gut wall.

• 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal)
• 12 pairs of cranial nerves
• Sensory (afferent) and motor (efferent) fibers; ganglia

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2. FUNCTIONS OF THE NERVOUS SYSTEM

1. Sensory input - Detects internal/external stimuli via receptors
2. Integration - Processes and interprets sensory information
3. Motor output - Activates effectors (muscles, glands)
4. Storage (memory) - Synaptic facilitation stores experiences
5. Homeostasis - ANS and hypothalamus regulate internal environment
6. Higher functions - Language, reasoning, emotion, consciousness

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3. SYNAPSE

Functional Anatomy

• Presynaptic terminal (bouton) - contains mitochondria and synaptic vesicles filled with neurotransmitter
• Synaptic cleft - 20-30 nm gap between membranes
• Postsynaptic membrane - contains receptor proteins + ion channels

Classification of Synapses

• Axodendritic (axon → dendrite) - most common
• Axosomatic (axon → cell body)
• Axoaxonic (axon → axon terminal) - modulates release
• Dendrodendritic

• Excitatory - produces EPSP (depolarization)
• Inhibitory - produces IPSP (hyperpolarization)

Synaptic Transmission (Chemical Synapse)

1. Action potential arrives at presynaptic terminal
2. Depolarization opens voltage-gated Ca²⁺ channels
3. Ca²⁺ influx triggers exocytosis of synaptic vesicles
4. Neurotransmitter diffuses across synaptic cleft
5. Binds to postsynaptic receptors
6. Ion channels open → EPSP or IPSP generated
7. Neurotransmitter removed by: reuptake, enzymatic degradation (e.g., AChE), or diffusion

Properties of Synapses

1. One-way conduction - chemical synapses conduct only presynaptic → postsynaptic
2. Synaptic delay - 0.5 ms (time for Ca²⁺ influx + exocytosis + diffusion)
3. Fatigue - repeated stimulation depletes vesicles
4. Summation - temporal (repeated stimuli) or spatial (multiple inputs) add up
5. Facilitation - subthreshold inputs bring membrane closer to threshold
6. Post-tetanic potentiation - increased transmission after high-frequency stimulation
7. Susceptibility to hypoxia, drugs, anesthetics - synapses are metabolically sensitive

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4. SENSORY MECHANISMS

Sensory Receptors

• Mechanoreceptors - touch, pressure, vibration, proprioception
• Thermoreceptors - temperature
• Nociceptors - pain
• Photoreceptors - light (rods and cones)
• Chemoreceptors - taste, smell, O₂/CO₂
• Osmoreceptors - osmolarity

• Exteroceptors - skin surface (touch, temperature, pain)
• Interoceptors - viscera
• Proprioceptors - muscles, joints, tendons (muscle spindles, GTOs, joint receptors)

• Free nerve endings - pain, temperature
• Encapsulated endings - Meissner's (light touch), Pacinian (vibration), Merkel's (sustained pressure), Ruffini's (skin stretch), Krause's (cold)

1. Specificity (Adequate stimulus) - each receptor responds best to one modality (labeled line principle)
2. Generator potential - graded depolarization proportional to stimulus intensity
3. Threshold - minimum stimulus to generate response
4. Adaptation - decline in firing rate with sustained stimulus
   • Rapidly adapting: Meissner, Pacinian (detect change/movement)
   • Slowly adapting: Merkel, Ruffini, nociceptors (detect sustained stimuli)
5. Receptive field - area of skin a single receptor serves; smaller = greater acuity

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Sensory Pathways: Ascending Tracts

A. Posterior Column (Dorsal Column-Medial Lemniscal) Tract

B. Lateral Spinothalamic Tract

C. Anterior Spinothalamic Tract

D. Trigeminal Pathway

• 1st neuron: Trigeminal ganglion (Gasserian ganglion)
• Modality-specific brainstem nuclei:
  • Fine touch/proprioception → Principal (Chief) sensory nucleus (pons) → crosses → medial lemniscus → VPM thalamus
  • Pain and temperature → Spinal trigeminal nucleus (descends to medulla/C2) → crosses → VPM thalamus
  • Proprioception (jaw) → Mesencephalic nucleus (unique - 1st order cell bodies in CNS)
• 3rd neuron: VPM thalamus → face area of somatosensory cortex (S1)

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5. SENSORY CORTEX AND SOMATIC SENSATIONS

Somatosensory Cortex (S1)

• Located in parietal lobe, postcentral gyrus (Brodmann Areas 3, 1, 2)
• Organized as a somatotopic map (sensory homunculus) - body regions mapped in proportion to receptor density, not body size
• Largest areas: hand (especially thumb), lips, tongue, face
• S2 (secondary somatosensory cortex) - in parietal operculum; receives bilateral input; important for learning and memory of tactile objects

Types of Somatic Sensations

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6. KINESTHETIC SENSATIONS

• Muscle spindles (Ia and II fibers) - sense muscle length and rate of length change
• Golgi tendon organs (Ib fibers) - sense muscle tension
• Joint receptors (Ruffini, Pacinian) - sense joint angle and movement
• Cutaneous mechanoreceptors - skin stretch

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7. PAIN SENSATION

Mechanism of Pain

Cutaneous Pain

• First pain (fast): Sharp, immediate; Aδ fibers; well localized
• Second pain (slow): Burning, delayed; C fibers; poorly localized; associated with suffering

Hyperalgesia

• Primary hyperalgesia: Increased sensitivity at site of injury (due to sensitization of peripheral nociceptors by prostaglandins, bradykinin)
• Secondary hyperalgesia: Increased sensitivity surrounding tissue (central sensitization in spinal cord - "wind-up")

Deep (Somatic) Pain

• Arises from muscles, tendons, joints, periosteum
• Carried mainly by C fibers
• Poorly localized, aching, diffuse
• Often accompanied by nausea, sweating, fall in blood pressure

Visceral Pain

• Arises from viscera (hollow organs - due to distension, ischemia, spasm; NOT cutting/burning)
• Poorly localized, dull, cramping
• Transmitted via sympathetic afferents (and parasympathetic for pelvic viscera)

• Visceral pain felt in a skin area remote from the viscus
• Mechanism (Convergence-Projection Theory): Visceral afferents converge on the same dorsal horn neurons as somatic afferents from the referred area; the brain interprets the signal as coming from the skin
• Examples:
  • Cardiac ischemia → left arm, jaw pain
  • Gallbladder → right shoulder (C3-C5 dermatome = referred via phrenic nerve)
  • Appendix → periumbilical initially, then right iliac fossa
  • Kidney → loin to groin
  • Diaphragmatic irritation → shoulder tip

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8. MOTOR CORTEX

Primary Motor Cortex (M1)

• Location: Precentral gyrus, frontal lobe (Brodmann Area 4)
• Contains Betz cells (giant pyramidal cells) - the largest neurons in the CNS
• Contains the motor homunculus - somatotopic map; hand and face have the largest representation
• Controls contralateral voluntary movements

Premotor Cortex

• Brodmann Area 6 (anterior to M1)
• Premotor area (lateral BA6) - plans movements based on sensory information; programs motor sequences
• Supplementary motor area (SMA, medial BA6) - involved in planning and initiating movements, especially bilateral sequences; active during mental rehearsal

Frontal Eye Field (Area 8) - Controls voluntary conjugate eye movements

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9. MOTOR PATHWAYS: DESCENDING TRACTS

A. Pyramidal (Corticospinal) Tracts

1. Descend through corona radiata → internal capsule (posterior limb, genu)
2. Cerebral peduncles (basis pedunculi) of midbrain
3. Pons (scattered into bundles by pontine nuclei)
4. Pyramids of medulla oblongata (hence "pyramidal")
5. Decussation of pyramids at junction of medulla and spinal cord (~85% cross)
6. Lateral corticospinal tract (crossed, 85%) - descends in lateral funiculus; controls distal limb movements (fine skilled movements)
7. Anterior corticospinal tract (uncrossed, 15%) - descends in anterior funiculus; controls proximal limb/trunk; eventually crosses in spinal cord

B. Extrapyramidal Tracts

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10. UPPER MOTOR NEURON (UMN) vs. LOWER MOTOR NEURON (LMN)

Paralysis Types

• Monoplegia - paralysis of one limb (UMN or LMN lesion)
• Paraplegia - paralysis of both lower limbs (spinal cord lesion below cervical level, e.g., thoracic cord injury)
• Hemiplegia - paralysis of one side (arm + leg) - UMN lesion above spinal cord, e.g., internal capsule stroke (contralateral body)
• Quadriplegia (Tetraplegia) - paralysis of all four limbs - cervical cord lesion (C1-C4 also affects respiration)

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11. MUSCLE TONE

• Gamma MN activates intrafusal fibers → maintains spindle sensitivity → Ia afferents discharge → activate alpha MN → slight contraction

• Tone is a spinal reflex, but modulated by descending pathways
• Facilitatory inputs: Vestibulospinal (extensors), pontine reticulospinal
• Inhibitory inputs: Medullary reticulospinal

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12. SPINAL CORD LESIONS

Complete Transection

• UMN signs emerge below lesion: spasticity, hyperreflexia, Babinski sign
• Autonomic dysreflexia (above T6 lesions)
• Mass reflex (triple withdrawal response)
• Bladder becomes automatic (reflex)
• All sensory modalities lost below lesion (bilateral)

Brown-Sequard Syndrome (Hemi-section)

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13. CEREBELLUM

Divisions and Functions

Layers of Cerebellar Cortex

1. Molecular layer (outer) - outer stellate cells, basket cells, Purkinje dendrites, parallel fibers (granule cell axons)
2. Purkinje cell layer (middle) - Purkinje cells; only output from cerebellar cortex; always inhibitory (GABA)
3. Granular layer (inner) - granule cells, Golgi II cells, glomeruli (mossy fiber synapses)

Cerebellar Ataxia

• Dysdiadochokinesia - inability to perform rapid alternating movements
• Ataxia - uncoordinated gait (wide-based, staggering, "drunken gait")
• Nystagmus - involuntary eye movements
• Intention tremor - tremor on purposeful movement (worsens near target)
• Scanning (staccato) speech - slurred, explosive dysarthria
• Hypotonia - decreased muscle tone

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14. POSTURE AND EQUILIBRIUM

Postural Reflexes (from lowest to highest)

• Stretch reflex - maintains muscle tone against gravity
• Flexor withdrawal reflex - protective
• Crossed extensor reflex - when one limb flexes, opposite extends for support

• Righting reflexes - return head/body to upright position
• Tonic neck reflexes (from proprioceptors in neck muscles):
  • Asymmetric tonic neck reflex: turning head → extension of ipsilateral limbs, flexion of contralateral
  • Symmetric tonic neck reflex: flexion of neck → flexion of forelimbs, extension of hindlimbs
• Labyrinthine righting reflex - inner ear orients head relative to gravity

• Righting reflexes - more complete body righting, including visual righting reflexes
• Placing and hopping reactions - anticipatory postural adjustments

• Voluntary postural adjustments - learned, anticipatory
• Visual postural control - visual cortex input integrates with other systems

• Vestibular apparatus (semicircular canals, utricle, saccule)
• Proprioceptors (muscle spindles, joint receptors)
• Visual system

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15. THALAMUS AND HYPOTHALAMUS

Thalamus - Nuclei and Functions

Thalamic Syndrome (Dejerine-Roussy Syndrome)

• Caused by infarction of the posterolateral thalamus (VPL)
• Features: Initial contralateral hemisensory loss, followed by thalamic pain - severe, burning, spontaneous pain on the contralateral side that is disproportionate to the stimulus (allodynia, hyperpathia)
• Also: Mild contralateral hemiplegia, hemiataxia, choreoathetosis

Hypothalamus - Functions

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16. RETICULAR FORMATION AND LIMBIC SYSTEM

Reticular Formation

1. Arousal and consciousness - ARAS activates thalamus → widespread cortical activation; damage → coma
2. Sleep-wake cycle - interacts with hypothalamus and thalamus
3. Muscle tone control - pontine RF facilitates, medullary RF inhibits muscle tone
4. Pain modulation - descending inhibition via periaqueductal gray (PAG) + nucleus raphe magnus; endogenous opioids (enkephalins, endorphins)
5. Cardiovascular control - vasomotor center (medullary RF)
6. Respiratory control - respiratory rhythm generation (pre-Bötzinger complex)
7. Vomiting center - located in medullary RF

Limbic System

• Hippocampus (memory consolidation)
• Amygdala (fear, aggression, emotional memory)
• Mammillary bodies
• Papez circuit (hippocampus → fornix → mammillary bodies → thalamus (anterior nucleus) → cingulate gyrus → entorhinal cortex → hippocampus)
• Cingulate gyrus (emotional processing, attention)
• Fornix (connects hippocampus to mammillary bodies)
• Also: Septal nuclei, olfactory cortex, hypothalamus, anterior thalamic nuclei

1. Emotional behavior (fear, rage, pleasure, aggression)
2. Memory - hippocampus is essential for consolidation of declarative (explicit) memory
3. Olfaction
4. Motivation and reward (mesolimbic dopamine system)
5. Visceral responses to emotion (via hypothalamus)
6. Sexual behavior

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17. BASAL GANGLIA

Structures (Components)

• Striatum = Caudate nucleus + Putamen (main INPUT station)
• Globus Pallidus = External (GPe) + Internal (GPi) (main OUTPUT station)
• Subthalamic nucleus (STN) - diencephalon
• Substantia Nigra = Pars compacta (SNc) + Pars reticulata (SNr)
• Ventral striatum (nucleus accumbens) - reward/motivation

Circuits (Direct vs. Indirect Pathways)

• D1 receptors in striatum → facilitates direct pathway (excitatory effect)
• D2 receptors in striatum → inhibits indirect pathway (also excitatory net effect)
• Overall: Dopamine facilitates movement

Parkinson's Disease

• Pathology: Degeneration of dopaminergic neurons in substantia nigra pars compacta (SNc) → ↓ dopamine in striatum
• Effect: Direct pathway underactive (less movement facilitation) + Indirect pathway overactive (more movement suppression) → net result: hypokinesia (poverty of movement)
• Lewy bodies (α-synuclein protein aggregates) in remaining neurons

• Tremor - resting tremor, "pill-rolling," 4-6 Hz, disappears with movement (unlike intention tremor of cerebellum)
• Rigidity - lead-pipe or cogwheel rigidity (due to increased tone in both agonists and antagonists)
• Akinesia/Bradykinesia - slowness, poverty of movement; reduced arm swing, masked facies
• Postural instability - loss of righting reflexes; festinating gait; falls

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18. CEREBRAL CORTEX

Lobes

Brodmann's Areas and Functions

Higher Functions: Learning and Memory

• Declarative (explicit) - facts and events; hippocampus-dependent; further divided into:
  • Semantic - general knowledge (facts)
  • Episodic - personal experiences
• Non-declarative (implicit) - skills, habits, conditioning; cerebellum, basal ganglia, amygdala-dependent

• Long-Term Potentiation (LTP) - persistent strengthening of synapses; NMDA receptor-dependent; basis of learning and memory
• Long-Term Depression (LTD) - weakening of synapses
• Repeated stimulation → Ca²⁺ influx through NMDA receptors → activates kinases (CaMKII) → AMPA receptor insertion → sustained potentiation

Speech Areas

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19. CEREBROSPINAL FLUID (CSF)

Formation

• Choroid plexus of lateral, third, and fourth ventricles (70-80%)
• Ependymal cells and brain parenchyma (20-30%)
• Rate: ~500 mL/day (total volume: ~150 mL; turnover ~3-4 times daily)
• Mechanism: Active secretion (Na⁺-K⁺-ATPase driven) of Na⁺ into ventricle → water follows osmotically

Composition

Circulation

Functions

1. Mechanical protection - buoyancy effect; reduces effective brain weight from 1400 g to ~25 g
2. Nutrient supply and waste removal - glucose, amino acids in; CO₂, metabolic waste out
3. Homeostasis of CNS environment - stable ionic composition
4. Neurohumoral communication - transport of peptides and hormones
5. Protection against infection (immune cells)

Lumbar Puncture (LP)

• Level: Between L3-L4 or L4-L5 intervertebral space (below the conus medullaris, which ends at L1-L2)
• Patient position: Lateral decubitus (fetal position) or sitting, flexed
• Layers traversed: Skin → subcutaneous → supraspinous ligament → interspinous ligament → ligamentum flavum → epidural space → dura mater → arachnoid → subarachnoid space

• Measure CSF pressure
• Diagnose meningitis, encephalitis (cells, protein, glucose, organisms)
• Diagnose subarachnoid hemorrhage (xanthochromia - yellow discoloration from bilirubin)
• Diagnose multiple sclerosis (oligoclonal bands, myelin basic protein)
• Intrathecal drug administration
• Diagnose Guillain-Barré syndrome (albuminocytologic dissociation: high protein, normal cells)

Blood-Brain Barrier (BBB)

• Formed by: Tight junctions between cerebral capillary endothelial cells + astrocyte foot processes (provide trophic support)
• Properties: Highly selective; lipid-soluble, small nonpolar molecules cross freely (O₂, CO₂, ethanol); glucose crosses via GLUT-1; ions cross poorly; large proteins cannot cross
• Areas without BBB (circumventricular organs): Area postrema (vomiting center), subfornical organ, organum vasculosum, neurohypophysis, pineal gland - these sense blood-borne signals
• Clinical: BBB broken in meningitis, tumors, trauma, stroke

Hydrocephalus

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20. AUTONOMIC NERVOUS SYSTEM (ANS)

Sympathetic Nervous System ("Fight or Flight")

• Paravertebral (sympathetic chain) ganglia - 22 pairs alongside spinal cord
• Prevertebral ganglia - celiac, superior mesenteric, inferior mesenteric (closer to organs)

• Preganglionic → ganglionic synapse: Acetylcholine (nicotinic receptors)
• Postganglionic → effector: Norepinephrine (adrenergic receptors); Exception: sweat glands = cholinergic; adrenal medulla (modified ganglion) releases epinephrine + NE directly into blood

Parasympathetic Nervous System ("Rest and Digest")

• Cranial: CN III (ciliary ganglion), CN VII (pterygopalatine + submandibular ganglia), CN IX (otic ganglion), CN X (vagus - ganglia in/near target organs)
• Sacral: S2, S3, S4 → pelvic splanchnic nerves → pelvic ganglia

• Both pre- and postganglionic: Acetylcholine
• Receptors on target: Muscarinic (M1-M5)

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21. EFFECTS OF EXERCISE ON BODY SYSTEMS

Effects on the Cardiovascular System

• ↑ Heart rate (HR) - sympathetic activation, withdrawal of vagal tone
• ↑ Stroke volume (SV) - increased venous return (Frank-Starling), ↑ inotropy
• ↑ Cardiac output (CO = HR × SV) - can increase from 5 L/min at rest to 20-25 L/min with maximal exercise
• ↑ Systolic BP - ↑ CO; diastolic BP little changed or decreases (vasodilation in muscles)
• Redistribution of blood flow - ↑ flow to skeletal muscle (up to 85%) and heart; ↓ flow to viscera and skin (early); ↑ to skin later (for heat dissipation)
• ↑ O₂ delivery and extraction (↑ a-vO₂ difference)
• ↑ Coronary blood flow (proportional to cardiac work)

• Athlete's heart:
  • Bradycardia at rest (↑ vagal tone, ↑ SV - so same CO with lower HR)
  • ↑ Left ventricular volume (eccentric hypertrophy - volume overload → ↑ SV)
  • ↑ Myocardial capillary density
  • ↑ Stroke volume
• Reduced resting BP (especially in hypertensives)
• ↑ Blood volume (↑ plasma volume early; ↑ RBC mass over weeks)
• Improved lipid profile (↑ HDL, ↓ triglycerides)

Effects on the Respiratory System

• ↑ Respiratory rate + ↑ Tidal volume → ↑ Minute ventilation (from 6-8 L/min at rest to 100-150 L/min maximal)
• ↑ O₂ uptake (VO₂) - can increase 15-20x above resting (VO₂ max = maximal O₂ consumption)
• ↑ CO₂ production - VCO₂ increases; drives hyperpnea
• Ventilation triggered by: ↑ CO₂, ↓ pH, ↑ K⁺, neural (central command + proprioceptive) factors
• At anaerobic threshold (lactate threshold): Lactic acid production → metabolic acidosis → additional respiratory stimulation → ventilation increases disproportionately (ventilatory anaerobic threshold)
• Improved O₂ diffusion - ↑ pulmonary blood flow → ↑ capillary recruitment → reduced dead space

• ↑ Respiratory muscle strength and endurance
• ↑ Lung diffusing capacity (DLCO) - more capillary recruitment/surface area
• Slight ↑ lung volumes (inspiratory reserve volume)
• Lower ventilation for same workload (improved efficiency)

Effects on the Musculoskeletal System

• ↑ Blood flow to active muscles (metabolic vasodilation: ↑ CO₂, ↓ O₂, ↑ adenosine, ↑ K⁺, ↓ pH, NO)
• ↑ Temperature in working muscle → right shift of oxyhemoglobin curve (Bohr effect) → better O₂ release
• Glycolysis and glycogenolysis for rapid ATP
• Delayed onset muscle soreness (DOMS) 24-48h post-exercise (micro-tears → inflammation)

• Aerobic training (endurance):
  • ↑ Mitochondrial density and oxidative enzymes (citrate synthase, etc.)
  • ↑ Type I (slow-twitch) fiber size and capillary density
  • ↑ Myoglobin content → better O₂ storage
  • ↑ Fat oxidation - spares glycogen (glycogen sparing)
  • ↑ Maximal oxygen uptake (VO₂ max)
  • ↑ Lactate threshold (ability to work harder before accumulating lactate)
• Resistance training (strength):
  • Hypertrophy of skeletal muscle fibers (especially Type II fast-twitch)
  • ↑ Myofibrillar protein (actin and myosin)
  • ↑ Muscle strength and power
  • Neural adaptations (improved motor unit recruitment, synchronization)
• Bone:
  • Weight-bearing exercise → ↑ bone mineral density (Wolff's law)
  • Prevents osteoporosis; increases periosteal bone formation
• Cartilage and tendons:
  • ↑ Tensile strength of tendons and ligaments
  • ↑ Synovial fluid production → better joint lubrication

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NERVOUS SYSTEM - PHYSIOLOGY

As per Sembulingam's Essentials of Medical Physiology (7th/8th Edition)

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CHAPTER 133 - ORGANIZATION OF THE NERVOUS SYSTEM

Central Nervous System (CNS)

Brainstem = Midbrain + Pons + Medulla oblongata

• Extends from foramen magnum to lower border of L1 vertebra
• Ends as conus medullaris; below this: cauda equina (horse's tail)
• Has 31 segments: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal
• Contains grey matter (H-shaped, neurons) and white matter (tracts)

Peripheral Nervous System (PNS)

1. Cranial nerves (12 pairs) - arise from brain
2. Spinal nerves (31 pairs) - arise from spinal cord

1. Somatic nervous system - voluntary control of skeletal muscles + somatic sensory input
2. Autonomic nervous system (ANS) - involuntary control of viscera, glands, smooth and cardiac muscle
   • Sympathetic division (thoracolumbar)
   • Parasympathetic division (craniosacral)

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FUNCTIONS OF THE NERVOUS SYSTEM

1. Sensory function - Collection of information from internal and external environment via sensory receptors
2. Integrative function - Processing and interpretation of sensory information; decision-making (mainly by brain)
3. Motor function - Sending commands to muscles and glands to bring about appropriate responses

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CHAPTER 140 - SYNAPSE

Definition

Functional Anatomy of a Synapse

1. Presynaptic terminal (synaptic knob/bouton):
   • Expanded end of axon of presynaptic neuron
   • Contains mitochondria (energy supply) and synaptic vesicles (neurotransmitter)
   • Presynaptic membrane has active zones for vesicle docking and fusion
2. Synaptic cleft:
   • Gap of 20-30 nm between pre- and postsynaptic membranes
3. Postsynaptic membrane:
   • Has receptor proteins specific for the neurotransmitter
   • Subsynaptic web beneath postsynaptic membrane

Classification of Synapses

1. Axodendritic - axon terminal contacts dendrite (most common)
2. Axosomatic - axon terminal contacts cell body (soma)
3. Axoaxonic - axon terminal contacts another axon terminal (modulates neurotransmitter release)
4. Dendrodendritic - dendrite to dendrite contact

1. Chemical synapse - uses neurotransmitters; most common in CNS; one-way transmission
2. Electrical synapse - gap junctions; ions pass directly; bidirectional; faster; found in cardiac muscle, smooth muscle, some brain areas

1. Excitatory synapse - produces EPSP (Excitatory Postsynaptic Potential) → depolarization
2. Inhibitory synapse - produces IPSP (Inhibitory Postsynaptic Potential) → hyperpolarization

Synaptic Transmission (Chemical Synapse - Steps)

1. Arrival of action potential at presynaptic terminal
2. Depolarization opens voltage-gated Ca²⁺ channels in presynaptic membrane
3. Ca²⁺ influx into terminal (from ECF)
4. Fusion of synaptic vesicles with presynaptic membrane → exocytosis
5. Neurotransmitter release into synaptic cleft
6. Diffusion of NT across cleft (20-30 nm gap)
7. Binding of NT to specific receptors on postsynaptic membrane
8. Ion channels open/close → change in postsynaptic membrane potential
   • If depolarization → EPSP → if threshold reached → action potential
   • If hyperpolarization → IPSP → inhibition
9. Termination of NT action by:
   • Re-uptake into presynaptic terminal (e.g., norepinephrine, dopamine)
   • Enzymatic degradation (e.g., acetylcholinesterase degrades ACh)
   • Diffusion away from cleft

Properties of Synapses (Sembulingam lists these specifically)

1. One-way conduction (Unidirectional transmission): Impulse travels only from presynaptic → postsynaptic (because neurotransmitter is only in presynaptic terminal and receptors only on postsynaptic membrane). This ensures nerve impulses do not travel backward.
2. Synaptic delay (Latent period): Time taken for transmission across synapse = 0.5 ms (0.3-0.5 ms). This delay is due to time needed for Ca²⁺ influx, vesicle movement, exocytosis, diffusion, and receptor binding.
3. Summation: Weak stimuli can be added together to generate an action potential:
   • Spatial summation - simultaneous stimulation of many presynaptic terminals
   • Temporal summation - repeated stimuli in quick succession at same synapse
4. Facilitation: Subthreshold stimuli make the postsynaptic neuron more excitable (partial depolarization). Does not produce action potential alone but lowers threshold for subsequent stimuli.
5. Occlusion: When two groups of fibers separately cause maximal excitation, their combined stimulation produces less effect than expected (sharing of postsynaptic neurons).
6. Subliminal fringe: Neurons near the discharge zone that are facilitated but not yet fired; represent the "reserve" for summation.
7. Post-tetanic potentiation: After a tetanic (rapid, repetitive) stimulus, subsequent stimuli produce greater postsynaptic response. Due to accumulation of Ca²⁺ in presynaptic terminal.
8. Fatigue: Prolonged stimulation at high frequency → decreased synaptic response due to depletion of neurotransmitter from vesicles.
9. Low oxygen susceptibility: Synaptic transmission is impaired by hypoxia because the process requires energy (ATP).
10. Effect of drugs: Synapses are sensitive to drugs:
    • Strychnine - blocks inhibitory synapses (glycine antagonist)
    • Caffeine - increases excitability
    • Benzodiazepines - enhance GABA → inhibitory
11. Convergence and Divergence:
    • Convergence: Many presynaptic neurons synapse on one postsynaptic neuron
    • Divergence: One presynaptic neuron synapses on many postsynaptic neurons

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CHAPTER 139 - SENSORY RECEPTORS

Definition

Classification of Sensory Receptors

1. Exteroceptors: Located on body surface; respond to external stimuli
   • Touch, pressure, temperature, pain, light, sound, smell, taste
2. Interoceptors (Visceroceptors): Located in visceral organs; respond to internal stimuli
   • Detect pressure, stretch, temperature, pain from organs
3. Proprioceptors: Located in muscles, tendons, joints; detect body position and movement
   • Muscle spindles, Golgi tendon organs, joint receptors, labyrinthine receptors

1. Mechanoreceptors - respond to mechanical deformation (touch, pressure, stretch, vibration)
2. Thermoreceptors - respond to temperature changes
3. Nociceptors (Pain receptors) - respond to painful stimuli (tissue damage)
4. Chemoreceptors - respond to chemical stimuli (taste, smell, O₂, CO₂, pH)
5. Photoreceptors - respond to light (rods and cones of retina)
6. Osmoreceptors - respond to osmotic pressure changes

1. Free nerve endings (non-encapsulated): Bare dendrites; detect pain, crude touch, temperature
2. Encapsulated nerve endings:
   • Meissner's corpuscles - light touch, two-point discrimination; fingertips, lips
   • Pacinian (Lamellar) corpuscles - vibration, deep pressure; rapidly adapting
   • Merkel's disc (Tactile disc) - sustained touch, pressure; slowly adapting
   • Ruffini endings - skin stretch, joint position; slowly adapting
   • Krause's end bulbs - cold temperature (some authors question this classification)
3. Specialized receptors: Hair cells (cochlea, vestibular), rods/cones, taste buds

Properties (Characteristics) of Sensory Receptors

1. Specificity (Adequate stimulus): Each receptor is maximally sensitive to one type of stimulus (e.g., Pacinian corpuscle for vibration). The specific stimulus that a receptor is most sensitive to is called its adequate stimulus. This is explained by the Labeled Line Principle.
2. Generator potential (Receptor potential): When a receptor is stimulated, a local, graded, non-propagated change in membrane potential is produced = generator potential. The magnitude is proportional to stimulus intensity. When generator potential reaches threshold at the first node of Ranvier, an action potential is generated.
3. Receptor threshold: Minimum intensity of stimulus needed to activate the receptor. Low threshold = high sensitivity.
4. Adaptation (Accommodation): Decrease in frequency of firing of a receptor despite constant stimulus application.
   • Rapidly adapting receptors (phasic): Fire at onset and offset of stimulus; detect change in stimulus intensity (e.g., Meissner's, Pacinian corpuscles, hair follicle endings)
   • Slowly adapting receptors (tonic): Fire throughout stimulus duration; detect sustained stimuli (e.g., Merkel's disc, Ruffini endings, pain receptors, muscle spindles)
5. Receptive field: The area of skin (or tissue) from which a single sensory unit can be activated. Smaller receptive field = greater spatial resolution/acuity (e.g., fingertip has small receptive fields and high acuity).

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CHAPTER 144 - SOMATOSENSORY SYSTEM AND SENSORY PATHWAYS

Types of Somatic Sensations (Sembulingam's Classification)

1. Touch (crude and fine/tactile)
2. Pressure
3. Temperature (hot and cold)
4. Pain

1. Tactile localization - ability to identify exact spot touched
2. Two-point discrimination (Tactile discrimination) - ability to distinguish two separate points simultaneously (normal fingertip: 2-3 mm; back: 40-70 mm)
3. Stereognosis - ability to recognize a 3D object by touch alone (without vision)
4. Vibratory sensation - detection of vibrating stimuli (tuning fork at 128 Hz or 256 Hz)
5. Graphesthesia - ability to recognize letters/numbers written on skin

The Ascending (Sensory) Tracts

1. Posterior Column Tract (Dorsal Column-Medial Lemniscal Pathway)

2. Lateral Spinothalamic Tract

3. Anterior Spinothalamic Tract

Sensory Pathway of Trigeminal Nerve

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SENSORY CORTEX AND SOMATIC SENSATIONS

Primary Somatosensory Cortex (S1)

• Location: Postcentral gyrus of parietal lobe (Brodmann Areas 3, 1, 2)
• Area 3a - receives proprioception from muscle spindles (Ia fibers via VPL)
• Area 3b - receives cutaneous mechanoreception (Meissner's and Merkel's)
• Area 1 - receives rapidly adapting cutaneous receptors (texture)
• Area 2 - receives pressure and joint position

• Located in parietal operculum (upper bank of lateral sulcus)
• Receives input from S1 and from thalamus
• Bilateral representation
• Important for learning by touch and tactile memory

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KINESTHETIC SENSATIONS

1. Muscle spindles (annulospiral endings - Ia, flower spray endings - II) - sense muscle length and rate of change of length
2. Golgi tendon organs (GTOs) - Ib fibers - sense muscle tension
3. Joint receptors (Ruffini, Pacinian) - sense joint angle and rate of movement
4. Cutaneous receptors (Meissner's, Ruffini) - sense skin stretch during movement

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CHAPTER 145 - PHYSIOLOGY OF PAIN

Definition

Pain Receptors (Nociceptors)

• Free nerve endings distributed throughout the body
• Respond to: mechanical, thermal, and chemical (polymodal) painful stimuli
• Algogenic (pain-producing) substances: Bradykinin (most potent), prostaglandins, histamine, serotonin, K⁺ ions, H⁺ ions, substance P, lactic acid

Cutaneous Pain

• Fiber: Aδ (Type A delta) - myelinated, small diameter, 6-30 m/s conduction velocity
• Quality: Sharp, pricking, well-localized
• Onset: Immediate
• Pathway: Neospinothalamic tract → VPL thalamus → somatosensory cortex (conscious localization)
• Function: Acute warning; triggers immediate withdrawal reflex

• Fiber: C fibers - unmyelinated, very small, 0.5-2 m/s conduction velocity
• Quality: Burning, aching, poorly localized, throbbing
• Onset: Delayed (0.5-1 second after fast pain)
• Pathway: Paleospinothalamic tract → intralaminar nuclei of thalamus → limbic system, hypothalamus, reticular formation, periaqueductal gray (PAG)
• Function: Prolonged suffering; drives autonomic and emotional responses

Mechanism of Pain Transmission (Sembulingam)

• Gate Control Theory (Melzack and Wall, 1965):
  • Substantia gelatinosa (SG) of dorsal horn acts as a "gate"
  • Large diameter (Aβ) fibers carrying touch CLOSE the gate → inhibit pain transmission
  • Small diameter (Aδ, C) fibers carrying pain OPEN the gate
  • This explains why rubbing an injured area reduces pain (activates Aβ fibers)
  • Descending control from brain can also modulate the gate

Hyperalgesia

• At the site of injury
• Due to peripheral sensitization - damaged tissue releases prostaglandins, bradykinin → lower threshold of nociceptors; sensitize C fibers
• Mediated by increased prostaglandin synthesis → therapeutic target of NSAIDs/aspirin

• In the area surrounding the injury (uninjured tissue)
• Due to central sensitization in dorsal horn neurons
• Mechanism: "Wind-up" - repeated C fiber activation → NMDA receptor activation → spinal cord neurons become hypersensitive

Deep Somatic Pain

• Origin: Muscles, bones, tendons, periosteum, joints
• Character: Diffuse, dull, aching, poorly localized; difficult to distinguish from visceral pain
• Accompanied by: Nausea, sweating, fall in blood pressure, muscle spasm (reflex muscle guarding)
• Pathway: Mainly C fibers

Visceral Pain

• Origin: Hollow viscera (distension, spasm, ischemia); NOT cutting or burning
• Character: Dull, cramping, poorly localized (visceral afferents = fewer in number, widely spaced)
• Pathway: Sympathetic afferents (most viscera); pelvic organs via parasympathetic (pelvic splanchnic)
• Associated with: Autonomic responses (nausea, vomiting, sweating, changes in BP and HR)

Referred Pain

• Visceral afferents and somatic afferents from the referred zone converge on the same second-order neurons in the dorsal horn
• The brain cannot distinguish between visceral and somatic input → interprets the signal as coming from the somatic (skin) area → pain is "referred" to skin

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MOTOR CORTEX AND DESCENDING TRACTS

Motor Cortex (Sembulingam - Chapter 152)

• Location: Precentral gyrus of frontal lobe - Brodmann Area 4
• Contains giant Betz cells (giant pyramidal cells, 60-80 μm) - largest neurons in CNS
• Arranged as motor homunculus - inverted map; hand and face have disproportionately large area
• Controls contralateral voluntary movements

• Brodmann Area 6 (anterior to M1)
• Lateral premotor area (PMC): Plans movements guided by external sensory cues
• Supplementary Motor Area (SMA) - medial Area 6: Plans self-initiated movements; active before voluntary movement begins (Bereitschaftspotential/readiness potential)

• Frontal Eye Fields (Area 8): Voluntary conjugate eye movements (saccades)
• Posterior parietal cortex (Areas 5, 7): Sensorimotor integration

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DESCENDING TRACTS

A. Pyramidal Tracts (Corticospinal + Corticobulbar)

Corticospinal Tract

• 60% from primary motor cortex (Area 4)
• 20% from premotor/SMA (Area 6)
• 20% from somatosensory cortex (Areas 3, 1, 2)

1. Corona radiata (white matter of cerebral hemisphere)
2. Posterior limb of internal capsule (anterior two-thirds - genu and posterior limb)
3. Basis pedunculi (cerebral peduncles) of midbrain - middle three-fifths
4. Pons - scattered into small bundles by transverse pontine fibers
5. Reunite in medulla to form pyramids
6. At junction of medulla and spinal cord: Pyramidal decussation (decussation of pyramids)
   • ~85% of fibers cross → Lateral corticospinal tract (LCS)
   • ~15% do not cross → Anterior corticospinal tract (ACS) - eventually cross at spinal level

Corticobulbar Tract

• Fibers from motor cortex → brainstem nuclei of cranial nerves (V, VII, IX, X, XI, XII)
• Most cranial nerve nuclei receive bilateral corticobulbar input
• Exception: Lower face (CN VII) and tongue (CN XII) → predominantly contralateral supply
• Clinical: Unilateral UMN lesion spares upper face (bilateral supply) but causes contralateral lower face weakness

B. Extrapyramidal Tracts

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UPPER MOTOR NEURON (UMN) vs LOWER MOTOR NEURON (LMN)

Paralysis

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MUSCLE TONE

Definition (Sembulingam)

Mechanism of Muscle Tone

1. Gamma motor neurons (fusimotor neurons) from ventral horn → intrafusal muscle fibers of muscle spindle
2. Gamma activation maintains spindle sensitivity
3. Ia afferents from muscle spindle → dorsal root → alpha motor neurons
4. Alpha MN → extrafusal muscle fibers → slight contraction = tone

• Facilitatory areas (increase tone): Pontine reticular formation + lateral vestibulospinal tract
• Inhibitory areas (decrease tone): Medullary reticular formation + cerebellum

Properties/Types of Altered Tone

• Flaccidity; muscle feels soft and doughy
• Causes: LMN lesion, cerebellar lesion, acute spinal shock, deep anesthesia
• Features: Decreased resistance to passive movement, pendular reflexes

• Causes: Severe LMN destruction, complete spinal shock
• Muscles completely flaccid, no response to stretch

1. Spasticity (Pyramidal/UMN): Velocity-dependent resistance to passive stretch; clasp-knife phenomenon (gives way suddenly like a penknife); affects antigravity muscles (flexors of arm, extensors of leg); deep reflexes brisk
2. Rigidity (Extrapyramidal/Basal ganglia): Resistance to passive stretch that is NOT velocity-dependent; present throughout range of movement; two types:
   • Lead-pipe rigidity: Uniform resistance throughout
   • Cogwheel rigidity: Ratchet-like, jerky resistance (Parkinson's disease = rigidity + tremor superimposed)

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SPINAL CORD LESIONS (Sembulingam - Chapter 143)

Complete Transection (Complete Cord Injury)

• Complete flaccid paralysis below level of lesion (bilateral)
• Complete loss of all sensory modalities below lesion (bilateral)
• Loss of all spinal reflexes (areflexia) below lesion
• Urinary retention (atonic bladder)
• Bowel retention (paralytic ileus)
• Loss of vasomotor control → hypotension
• Priapism (paradoxical - loss of sympathetic)
• Duration: Days to 3-6 weeks (longer in humans than animals)

• Return of spinal reflexes (exaggerated → hyperreflexia)
• Spasticity develops
• Babinski sign becomes positive
• Automatic (reflex) bladder develops
• Mass reflex (triple flexion reflex) → powerful noxious stimulus below lesion triggers: bilateral flexion of lower limbs + evacuation of bladder and bowel + profuse sweating
• Autonomic dysreflexia (lesions above T6) → massive sympathetic discharge below lesion triggered by stimuli (full bladder, etc.) → hypertensive crisis, bradycardia (dangerous)

Brown-Séquard Syndrome (Hemisection of Spinal Cord)

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CHAPTER 150 - CEREBELLUM

Functions (Sembulingam)

1. Coordination of voluntary movements - ensures smooth, accurate, purposeful movements (timing, sequencing, coordination)
2. Regulation of muscle tone - via connections with reticulospinal and vestibulospinal tracts (generally decreases tone)
3. Maintenance of posture and equilibrium - vestibulocerebellum; coordinates with vestibular apparatus
4. Coordination of eye movements
5. Motor learning - stores learned motor skills; climbing fiber-LTD

Divisions

• Superior cerebellar peduncle (brachium conjunctivum): Main OUTPUT - dentate nucleus → contralateral red nucleus and VL thalamus → motor cortex
• Middle cerebellar peduncle (brachium pontis): Input from contralateral pontine nuclei (corticopontocerebellar)
• Inferior cerebellar peduncle (restiform body): Input from spinal cord (spinocerebellar tracts), inferior olivary nucleus (climbing fibers), vestibular nuclei

Cerebellar Cortex Layers

Cerebellar Ataxia (Signs of Cerebellar Lesion)

1. Dysmetria: Inability to judge distance; past-pointing (overshot or undershoot target) in finger-nose-finger test
2. Ataxia: Incoordination; wide-based, staggering, "drunken" gait (truncal ataxia = vermis lesion; limb ataxia = hemisphere lesion)
3. Nystagmus: Involuntary rhythmic eye oscillations; towards side of lesion
4. Intention tremor: Tremor that appears/worsens during voluntary movement (not at rest); worsens as limb approaches target
5. Dysdiadochokinesia: Inability to perform rapid alternating movements (e.g., pronation-supination)
6. Scanning (staccato) dysarthria: Slurred, explosive, irregular speech
7. Hypotonia: Decreased muscle tone; pendular knee jerk
8. Rebound phenomenon (Loss of check reflex): Cannot halt a movement when resistance is suddenly removed (forearm flexion against resistance - when resistance removed, forearm hits the face)
9. Romberg test: Negative in cerebellar ataxia (ataxia present even with eyes OPEN; does not significantly worsen with eye closure). This distinguishes from sensory/posterior column ataxia (Romberg positive = worse with eyes closed).

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CHAPTER 157 - POSTURE AND EQUILIBRIUM

Postural Reflexes Classification (Sembulingam's Classification)

• Stretch reflex (Myotatic reflex): Maintains tone against gravity; monosynaptic
• Positive supporting reaction: Pressure on sole → extension of lower limb (supports weight)
• Crossed extensor reflex: Flexion of one limb → extension of opposite limb

• Tonic neck reflexes (TNR):
  • Asymmetric TNR: Rotation of head → extension of limbs on side toward which face turns (jaw limbs extend; skull limbs flex)
  • Symmetric TNR: Flexion of neck → forelimb flexion + hindlimb extension; extension of neck → reverse
• Tonic labyrinthine reflexes: Changes in head position in space → changes in extensor tone (via otolith organs)
• Righting reflexes (medullary): Labyrinthine righting reflex → orients head upright; body righting reflex acting on head

• Complete righting reflexes - full body righting; need intact midbrain + vestibular apparatus + vision
• Optical righting reflex - visual cues orient head/body
• Placing and hopping reactions

• Voluntary postural adjustments - learned, anticipatory
• Cortical placing reaction - visual-guided placement of limb

1. Vestibular system (semicircular canals for angular acceleration; utricle and saccule for linear acceleration and gravity)
2. Proprioceptive system (muscle spindles, joint receptors)
3. Visual system

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CHAPTER 147 - THALAMUS

Nuclei and Functions

Thalamic Syndrome (Dejerine-Roussy Syndrome)

• Cause: Thalamic infarction (most commonly posterior thalamus - thalamogeniculate artery territory)
• Features:
  • Initial contralateral hemisensory loss (all modalities)
  • Followed by thalamic pain - severe, persistent, burning, spontaneous contralateral pain; disproportionate to stimulus; hyperpathia (exaggerated response) and allodynia (pain to non-painful stimuli)
  • Mild contralateral hemiplegia
  • Hemiataxia
  • Choreoathetosis (involuntary movements)
• Mechanism: Loss of normal sensory gating → thalamus generates spontaneous pain signals

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CHAPTER 149 - HYPOTHALAMUS

Nuclei and Functions (Sembulingam)

1. Defense reaction (rage, fear - via limbic connections)
2. Drinking (thirst center in lateral hypothalamus)
3. Diet (feeding and satiety)
4. Dynamo (ANS control - sympathetic and parasympathetic)
5. Diuresis (ADH regulation, water balance)
6. Also: Pituitary control (releasing/inhibiting hormones), thermoregulation, sleep-wake cycle, circadian rhythms, sexual behavior

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CHAPTER 154 - RETICULAR FORMATION

Components

• All sensory pathways send collateral branches to ARAS
• ARAS sends diffuse projections to the entire cerebral cortex via thalamus (intralaminar nuclei)
• Maintains wakefulness and alertness (consciousness)

• Pontine (medial) RF → facilitates spinal motor neurons (extensors)
• Medullary (lateral) RF → inhibits spinal motor neurons

Functions of Reticular Formation

1. Arousal and consciousness: ARAS maintains wakefulness; damage → coma
2. Sleep-wake cycle: Interacts with hypothalamic sleep center
3. Control of muscle tone: Facilitatory and inhibitory centers
4. Pain modulation: Periaqueductal gray (PAG) + Nucleus Raphe Magnus → descending inhibition of pain via enkephalins and serotonin (endogenous analgesia system)
5. Cardiovascular control: Vasomotor center (medullary RF) - pressor and depressor areas
6. Respiratory control: Respiratory rhythm generation (pre-Bötzinger complex in medulla)
7. Vomiting: Emetic center in medullary RF
8. Habituation and attention

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CHAPTER 153 - LIMBIC SYSTEM

Components (Broca's "Le Grand Lobe Limbique" - ring of cortex)

• Cingulate gyrus (above corpus callosum)
• Parahippocampal gyrus
• Hippocampus + dentate gyrus (archicortex)
• Entorhinal cortex (area 28)
• Olfactory cortex (piriform cortex)

• Amygdala (amygdaloid complex)
• Septal nuclei
• Anterior thalamic nuclei
• Hypothalamus (mammillary bodies)
• Fornix (major white matter pathway)

Functions of Limbic System (Sembulingam)

1. Emotional behavior: Fear, rage, aggression, pleasure (amygdala is key)
2. Memory: Hippocampus essential for consolidation of declarative memory (short-term → long-term memory)
3. Olfaction (piriform cortex)
4. Autonomic and somatic responses to emotion (via hypothalamus)
5. Feeding behavior and appetite
6. Sexual behavior and reproduction
7. Motivation and reward (nucleus accumbens - mesolimbic dopamine)
8. Sleep-wake cycle modulation

• Psychic blindness (visual agnosia)
• Hypersexuality
• Hyperorality (puts everything in mouth)
• Emotional blunting (placidity, tameness - no fear or aggression)
• Dietary changes (dietary indiscretion)

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CHAPTER 151 - BASAL GANGLIA

Components (Sembulingam)

• Corpus striatum:
  • Neostriatum = Caudate nucleus + Putamen (main INPUT - receive from cortex)
  • Paleostriatum = Globus pallidus (internal GPi + external GPe) (main OUTPUT)
• Subthalamic nucleus (STN) - diencephalon
• Substantia nigra - Pars compacta (SNc) + Pars reticulata (SNr)
• Amygdaloid nucleus (some classifications include)

Circuits

Functions of Basal Ganglia (Sembulingam)

1. Control and execution of voluntary movements (especially learned, automatic, sequential)
2. Regulation of automatic associated movements (e.g., arm swing during walking)
3. Control of muscle tone
4. Postural control
5. Cognitive functions (via caudate-prefrontal circuit)

Parkinson's Disease

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CHAPTER 152 - CEREBRAL CORTEX

Lobes and Key Areas

Brodmann's Areas and Functions (Sembulingam)

Higher Functions

Learning and Memory (Chapter 162)

• Temporary storage (seconds to minutes)
• Maintained by reverberating circuits (self-re-exciting loops)
• Limited capacity (7 ± 2 items, Miller's Law)

• Declarative (Explicit):
  • Semantic memory (facts, knowledge)
  • Episodic memory (personal experiences)
  • Requires hippocampus for consolidation
• Non-declarative (Implicit):
  • Procedural memory (skills, habits) - basal ganglia, cerebellum
  • Conditioning - amygdala (emotional conditioning), cerebellum (motor conditioning)

• Long-Term Potentiation (LTP): Repeated stimulation → NMDA receptor activation → Ca²⁺ influx → kinase activation → insertion of more AMPA receptors → strengthened synapse → basis of learning and memory
• Long-Term Depression (LTD): Weakening of synaptic connections (important for cerebellar motor learning)

Speech

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CHAPTER 163 - CEREBROSPINAL FLUID (CSF)

Formation

• Site: Choroid plexus of the lateral, third, and fourth ventricles (70-80%); remainder from ependymal cells
• Rate: 500 mL/day formed; total volume = ~150 mL (turnover 3-4 times/day)
• Mechanism: Active secretion - Na⁺-K⁺-ATPase pumps Na⁺ into ventricle → Cl⁻ and HCO₃⁻ follow → water follows osmotically

Composition (Sembulingam's Table)

Circulation of CSF (Sembulingam's Flow)

Lateral ventricles
        ↓ (via Foramen of Monro = Interventricular foramen)
Third ventricle
        ↓ (via Aqueduct of Sylvius = Cerebral aqueduct)
Fourth ventricle
        ↓ (via Foramen of Magendie - median + Foramina of Luschka - 2 lateral)
Subarachnoid space (around brain and spinal cord)
        ↓
Arachnoid villi/granulations (Pacchionian granulations) → Superior sagittal sinus → Venous blood

Functions of CSF

1. Protection (mechanical): Buoyancy - reduces effective weight of brain from 1400 g to 25 g; cushions brain from jolts
2. Nutrition: Carries glucose and amino acids; removes metabolic waste (CO₂, lactic acid)
3. Maintenance of uniform environment: Stable ionic composition for neurons
4. Regulation of intracranial pressure
5. Neurohumoral communication
6. Lymphatic equivalent for CNS (immune surveillance via lymphocytes)

Lumbar Puncture (LP)

1. Skin
2. Subcutaneous fat
3. Supraspinous ligament
4. Interspinous ligament
5. Ligamentum flavum
6. Epidural (extradural) space
7. Dura mater
8. Subdural space (potential)
9. Arachnoid mater
10. Subarachnoid space ← CSF obtained here

• Measure CSF pressure (normal 70-180 mm H₂O)
• Diagnose meningitis (↑ cells, ↓ glucose, ↑ protein; organisms on culture)
• Diagnose viral encephalitis (↑ lymphocytes, normal glucose)
• Diagnose subarachnoid hemorrhage (xanthochromia - yellow CSF; RBCs)
• Diagnose TB meningitis (very low glucose, high protein, lymphocytes, fibrin clot)
• Diagnose MS (oligoclonal bands, ↑ IgG, myelin basic protein)
• Diagnose Guillain-Barré Syndrome (albuminocytologic dissociation: ↑↑ protein, normal cells)
• Spinal anesthesia/intrathecal drug administration
• Queckenstedt's test: compress jugular vein → rise in CSF pressure (normal); no rise = spinal block

Blood-Brain Barrier (BBB)

• Maintains stable ionic environment for neuronal function
• Prevents entry of harmful substances, large molecules, pathogens
• Selective - allows: O₂, CO₂, glucose (GLUT-1), lipid-soluble substances, water, ethanol
• Blocks: Proteins, polar molecules, many drugs, most antibiotics (exception: chloramphenicol, rifampicin, metronidazole)

• Area postrema (vomiting center - "senses" emetogenic substances in blood)
• Subfornical organ, organum vasculosum of lamina terminalis (osmoreception)
• Neurohypophysis, pineal gland, adenohypophysis

Hydrocephalus

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CHAPTER 164 - AUTONOMIC NERVOUS SYSTEM (ANS)

Sympathetic Nervous System

• Paravertebral (sympathetic chain) ganglia - 22 pairs
• Prevertebral ganglia - celiac, superior/inferior mesenteric, aorticorenal

• Preganglionic: Acetylcholine (nicotinic N₁ receptors)
• Postganglionic: Norepinephrine (adrenergic α and β receptors)
• Exception: Sweat glands = cholinergic (muscarinic); adrenal medulla releases epinephrine + NE

Parasympathetic Nervous System

• Cranial - CN III (Edinger-Westphal nucleus → ciliary ganglion), CN VII (superior salivatory nucleus → pterygopalatine + submandibular ganglia), CN IX (inferior salivatory nucleus → otic ganglion), CN X (dorsal motor nucleus → ganglia in/near target organs)
• Sacral - S2, S3, S4 → pelvic splanchnic nerves

Comparison - Sympathetic vs. Parasympathetic (Sembulingam's Table)

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EFFECTS OF EXERCISE ON BODY SYSTEMS

Effects on the Cardiovascular System

• ↑ Heart rate (HR): Sympathetic activation (↑ NE/epinephrine) + withdrawal of vagal tone
• ↑ Stroke volume (SV): Increased venous return → Frank-Starling mechanism + increased inotropy (↑ catecholamines)
• ↑ Cardiac output (CO = HR × SV): From 5 L/min (rest) → up to 20-25 L/min (maximal exercise)
• ↑ Systolic BP: ↑ CO; diastolic minimally changed or falls (peripheral vasodilation in muscles)
• Redistribution of blood: ↑ to skeletal muscle (15-20% at rest → up to 85% with exercise) and heart; ↓ to viscera, kidneys, skin (early); ↑ to skin later for heat dissipation
• ↑ Oxygen consumption (VO₂): Can increase 15-20 times above resting

• Athlete's heart:
  • Resting bradycardia (↑ vagal tone + ↑ SV)
  • Eccentric LV hypertrophy (increased volume)
  • ↑ Stroke volume at rest and exercise
• ↑ Blood volume (plasma volume first, then RBC mass)
• ↑ Maximum cardiac output (↑ VO₂ max)
• Improved lipid profile (↑ HDL, ↓ LDL, ↓ triglycerides)
• ↓ Resting BP (beneficial in hypertension)

Effects on the Respiratory System

• ↑ Rate and depth of breathing → ↑ Minute ventilation (VE): From 6-8 L/min (rest) → up to 100-150 L/min (maximal)
• ↑ VO₂ (O₂ uptake) and VCO₂ (CO₂ output)
• Stimuli for increased ventilation: ↑ CO₂ (main), ↓ pH, ↑ K⁺, ↑ body temperature, proprioceptive input from exercising muscles, central command
• At anaerobic threshold (lactate threshold): Anaerobic glycolysis → lactic acid → metabolic acidosis → excess CO₂ → steep rise in ventilation (ventilatory anaerobic threshold/VT)
• Improved O₂ diffusion: ↑ pulmonary capillary recruitment → ↑ surface area

• ↑ Respiratory muscle strength
• ↑ Pulmonary diffusing capacity (DLCO)
• Lower ventilation at same workload (efficiency)
• ↑ Tidal volume (predominantly, not rate)

Effects on the Musculoskeletal System

• ↑ Local blood flow (metabolic vasodilation)
• ↑ Temperature → right shift of O₂-Hb dissociation curve (Bohr effect) → ↑ O₂ release to tissues
• Glycogenolysis for rapid ATP; at higher intensities: anaerobic glycolysis → lactic acid
• DOMS (Delayed Onset Muscle Soreness) 24-72 hours post-exercise

• ↑ Mitochondrial density and size (most important adaptation)
• ↑ Oxidative enzymes (citrate synthase, succinate dehydrogenase)
• ↑ Capillary density (better O₂ delivery)
• ↑ Myoglobin content (O₂ storage)
• Selective hypertrophy of Type I (slow-twitch) fibers
• Glycogen sparing (increased fat oxidation)
• ↑ Lactate threshold and ↑ VO₂ max

• Hypertrophy of Type II (fast-twitch) fibers
• ↑ Myofibrillar proteins (actin, myosin)
• ↑ Muscle strength, power, and endurance
• Neural adaptation (improved motor unit recruitment and synchronization)
• ↑ Bone mineral density (Wolff's law - mechanical load stimulates osteoblasts)
• ↑ Tendon and ligament tensile strength

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