Chapter 12 – Nervous System Comprehensive Study Notes (copy)
Nervous System: Core Purposes and High-Level Roles
Communication & control super-system linking body and mind.
Collects information
Receptors scattered throughout body detect internal & external stimuli.
Sensory (afferent) signals travel via nerves toward spinal cord & brain.
Processes & evaluates information
CNS (brain + spinal cord) integrates data, compares to memory/homeostatic set-points and decides on responses.
Initiates responses
Motor (efferent) output sent through peripheral nerves to effectors (muscle or gland cells) that carry out actions such as muscle contraction or hormone secretion.
Underpins consciousness, reflexes, learning, homeostasis and survival behaviors.
Structural & Functional Organization
Structural split
Central Nervous System (CNS): brain + spinal cord (integration centers).
Peripheral Nervous System (PNS): nerves (axon bundles) + ganglia (PNS cell-body clusters).
Functional split
Sensory (afferent) division → “Input”
Somatic sensory: consciously perceived (skin, eyes, ears, proprioceptors).
Visceral sensory: usually unconscious (blood pressure, CO₂ levels, stretch of GI tract, kidneys, heart).
Motor (efferent) division → “Output”
Somatic motor: voluntary control of skeletal muscle.
Autonomic/Visceral motor: involuntary control of cardiac muscle, smooth muscle & glands.
Sympathetic (fight/flight) & Parasympathetic (rest/digest) subdivisions coordinate opposite physiologic states.
Neurons – Fundamental Cellular Units
General Characteristics
Excitability – membrane potential changes when stimulated.
Conductivity – electrical signals propagated along membrane via sequential opening of voltage-gated channels.
Secretion – release of neurotransmitters (NTs) at synapses.
Extreme longevity – often survive > 100 years.
Amitotic – most lose mitotic ability after fetal development (clinical consequence: limited replacement after injury).
Detailed Structure
Cell body (soma/perikaryon)
Contains nucleus, organelles, ribosome-rich chromatophilic (Nissl) bodies → intensive protein synthesis.
Initiates or integrates graded potentials.
Dendrites
Short, tapering, highly branched, unmyelinated.
Receive synaptic input; greater number = larger surface area for information.
Axon
Single long process (may branch as axon collaterals → telodendria → synaptic knobs).
Attaches at axon hillock; cytoplasm = axoplasm; membrane = axolemma.
Synaptic knobs house vesicles filled with NT; release on arrival of action potential.
Cytoskeleton
Microfilaments + microtubules + neurofilaments → bundled into neurofibrils providing tensile strength (like steel cables running length of axon).
Axonal Transport
Provides bidirectional "railway" for organelles, enzymes, toxins, viruses.
Fast transport (~400 mm/day)
Uses ATP-powered motor proteins along microtubules.
Anterograde: vesicles, mitochondria, membrane proteins.
Retrograde: used vesicles, growth factors, sometimes pathogens (e.g., rabies virus) → clinical relevance.
Slow transport (0.1–3 mm/day)
Axoplasmic flow; only anterograde; carries enzymes, cytoskeletal subunits.
Classification
Structural
Multipolar (many dendrites, 1 axon) – majority, incl. all motor neurons.
Bipolar (1 dendrite, 1 axon) – rare, retina & olfactory epithelium.
Unipolar (pseudounipolar) – sensory neurons; single process splits into peripheral & central branches.
Anaxonic – dendrites, no axon; interneurons in CNS; modulate local circuits.
Functional
Sensory/afferent → mostly unipolar; convey input to CNS.
Motor/efferent → all multipolar; convey output from CNS.
Interneurons → 99 % of neurons; analysis & integration; shapes reflexes & higher cognition.
Nerves & Connective Tissue Organization
Nerve = bundle of parallel axons in PNS (analogous to multi-conductor cable).
Connective wrappings:
Epineurium – dense irregular CT, encloses entire nerve incl. blood vessels.
Perineurium – dense irregular CT around each fascicle (axon bundle); forms blood-nerve barrier.
Endoneurium – delicate areolar CT around each axon; electrically insulates.
Classification
Cranial vs. spinal (origin).
Sensory, motor, or mixed (function). Majority of named nerves are mixed though each individual axon transmits only one modality.
Synapses – Where Neurons Communicate
Electrical synapses – rare; gap junctions; virtually no delay (e.g., some eye & brainstem nuclei for rapid synchronous activity).
Chemical synapses – predominant; ~0.3–5 ms synaptic delay.
AP arrives at presynaptic knob.
\text{Ca^{2+}} influx via voltage-gated channels.
Vesicle fusion & NT exocytosis.
NT diffuses across cleft (≈30 nm) & binds postsynaptic receptors → graded potential.
Termination by enzymatic degradation, reuptake, or diffusion away.
Glial (Neuroglial) Cells – Support Squad
CNS Glia
Astrocytes (most abundant)
Perivascular feet form Blood-Brain Barrier (BBB) regulating substance entry.
Regulate extracellular K⁺ & neurotransmitter levels; recycle NT.
Provide structural framework, guide neuronal migration, fill space of dead neurons (form scar tissue → obstacle to regeneration).
Ependymal cells
Line ventricles & central canal; with capillaries form choroid plexus → secrete & circulate cerebrospinal fluid (CSF) via cilia.
Microglia
Immune, phagocytic; remove debris & pathogens; act as CNS "janitors" & antigen-presenting cells.
Oligodendrocytes
Myelinate CNS axons; single cell wraps segments of many axons; speeds conduction & conserves energy.
PNS Glia
Satellite cells: surround cell bodies in ganglia; regulate nutrient/waste exchange; electrical insulation.
Neurolemmocytes (Schwann cells): myelinate single 1 mm segments of PNS axons; produce neurilemma vital for regeneration.
Myelination
Myelin = multiple concentric layers of glial plasma membrane (high lipid → glossy white).
PNS: Schwann cell wraps only one small segment; outermost layer with cytoplasm & nucleus called neurilemma; gaps → nodes of Ranvier (neurofibril nodes).
CNS: Oligodendrocyte projects to many axons; no neurilemma.
Unmyelinated fibers: In PNS, multiple axons sit in Schwann cell groove without full wrapping; in CNS, bare.
Demyelinating Disorders (Clinical)
Multiple Sclerosis (MS): autoimmune attack on CNS myelin; scarring → conduction block; variable sensory & motor deficits.
Guillain-Barré Syndrome: acute autoimmune demyelination of PNS; ascending muscle weakness; often reversible.
Axon Regeneration
PNS: possible if soma intact & some neurilemma remains.
Success ↑ when damage minimal & distance to target short.
Axon severed.
Distal segment undergoes Wallerian degeneration; proximal swells.
Neurilemma + endoneurium create regeneration tube.
Schwann cells secrete nerve growth factors guiding new axon.
Reinnervation restores function.
CNS: poor regeneration due to oligodendrocyte inhibitory molecules, axon crowding, and astrocytic scar tissue.
Membrane Proteins: Pumps & Channels
Pumps: active transport against gradient; require ATP.
\text{Na}^+/\text{K}^+ pump moves 3 \text{Na}^+ out / 2 \text{K}^+ in → maintains gradients & adds \approx -3\,\text{mV} to RMP.
\text{Ca}^{2+} pumps keep intracellular calcium low.
Channel types
Leak (passive) – always open (e.g., K⁺ leak channel critical for RMP).
Chemically gated – open when NT binds (on dendrites/soma).
Voltage-gated – open/close with membrane potential (dense on axon & bouton). \text{Na}^+ channel has 3 states: resting, activation, inactivation.
Modality-gated – respond to physical stimuli (pressure, light, temperature) in sensory receptors.
Electrical Foundations – Ohm’s Law & RMP
Ohm’s Law: I = \dfrac{V}{R}.
Resting Membrane Potential (RMP) ≈ -70\,\text{mV}.
Driven primarily by K⁺ efflux (chemical gradient) limited by negative interior (electrical gradient).
Presence of some Na⁺ leak (inward) shifts equilibrium from -90\,\text{mV} (K⁺ only) to -70\,\text{mV}.
Na⁺/K⁺ pump maintains gradients long-term and uses up to 70 % of neuronal ATP (high metabolic demand – explains vulnerability to hypoxia).
Signal Reception – Graded Potentials (Receptive Segment)
EPSP (excitatory): usually Na⁺ or Ca²⁺ entry → depolarization.
IPSP (inhibitory): K⁺ exit or Cl⁻ entry → hyperpolarization.
Properties: variable amplitude, decremental, short-lived, can sum.
Integration – Summation at the Axon Hillock (Initial Segment)
Spatial summation: simultaneous input at multiple locations.
Temporal summation: rapid succession from one presynaptic neuron.
Threshold: ~-55\,\text{mV} needed to open voltage-gated Na⁺ channels → all-or-none firing rule (like pulling a trigger, extra force doesn’t make bullet faster).
Action Potentials & Propagation (Conductive Segment)
Phases
Resting: all voltage-gated channels closed.
Depolarization: Na⁺ channels open, Na⁺ rushes in, membrane to +30\,\text{mV}.
Repolarization: Na⁺ channels inactivate; K⁺ channels open, K⁺ exits.
Hyperpolarization: K⁺ channels slow to close → membrane dips to \approx -80\,\text{mV}.
Return to RMP by leak & pumps.
Refractory periods
Absolute (~1 ms): no second AP possible (Na⁺ inactivation gates).
Relative: stronger stimulus can fire (membrane hyperpolarized).
Conduction modes
Continuous (unmyelinated): every segment undergoing full AP; slower & energy costly.
Saltatory (myelinated): APs only at nodes; internodal charge flow fast; velocity ↑ & ATP cost ↓.
Velocity & Frequency
Speed increases with axon diameter & myelination.
Group A: large, myelinated, \le 150\,\text{m/s} (somatic motor, proprioception).
Group B: small, myelinated, ~15 m/s; Group C: small, unmyelinated, ~1 m/s (visceral pain, autonomic motor).
Stimulus intensity encoded by frequency (spikes/sec), not amplitude; ceiling set by refractory period.
Neurotransmitters
~100 identified; stored in vesicles; release triggered by \text{Ca^{2+}}.
Chemical Classes
Acetylcholine (ACh) – prototype; at NMJ, autonomic ganglia, CNS arousal.
Biogenic amines: catecholamines (dopamine, norepinephrine, epinephrine), indolamines (serotonin, histamine).
Amino acids: glutamate (major CNS excitatory), GABA & glycine (inhibitory).
Neuropeptides: endorphins (analgesia), substance P (pain), neuropeptide Y (appetite).
Functional Classes
Excitatory vs. inhibitory (depends on receptor subtype).
Direct (ionotropic) vs. indirect (metabotropic, G-protein/2nd messenger).
Acetylcholine Lifecycle Example
Synthesized from choline + acetate → stored in vesicles.
Released into cleft by exocytosis.
Binds nicotinic (ligand-gated cation channel → EPSP) or muscarinic (G-protein, slower EPSP/IPSP).
Cleared by acetylcholinesterase → acetate + choline; choline recycled.
Drugs: Curare blocks nicotinic receptors (paralysis); Organophosphates inhibit AChE (toxicity); Galantamine (AChE inhibitor) treats Alzheimer’s; SSRIs reduce serotonin reuptake (mood).
Neuromodulators
Produce longer-lasting, widespread effects.
Nitric oxide (NO): gaseous; retrograde messenger; vasodilator in PNS (e.g., erectile function).
Endocannabinoids: lipid-based; modulate memory, appetite; mimic THC.
Facilitation vs. Inhibition at synapses adjusts responsiveness by altering NT release or receptor density.
Neural Circuits / Pools – Information Routing Architectures
Converging: many inputs → one output (e.g., multiple senses → salivary nucleus → salivation).
Diverging: one input → many outputs (e.g., motor cortex → multiple muscle groups for walking).
Reverberating: feedback loop sustains activity (e.g., respiratory center rhythm during sleep).
Parallel-after-discharge: input diverges then reconverges with different delays → complex higher-order calculations (possible role in problem solving).
Tumors & Pathology Insight
Primary brain tumors often arise from mitotically active support cells (meninges, glia) → e.g., gliomas; may be benign or malignant capable of metastasis.
Illustrates importance of glial mitotic control and blood-brain barrier in oncology.
Ethical & Practical Implications:
Understanding conduction & regeneration drives neuroprosthetics and rehabilitation (e.g., nerve grafts using Schwann cell tubes).
Knowledge of demyelinating diseases informs strategies for immunomodulation & remyelination therapies.
Drug design targeting specific NT clearance (SSRIs) or receptor subtype (nicotinic vs. muscarinic) must consider synaptic dynamics & side-effects.
Advances in neuromodulators (endocannabinoids, NO) raise societal discussions around cannabis use, cognitive enhancement, and vascular health.