Chapter 7 – Nervous System Study Guide

Types of Neurons and Supporting Cells

• Neurons: structural / functional units of the nervous system
• Common anatomy: cell body (soma), dendrites, single axon.
• Functional classes:
– Sensory (Afferent) Neurons
• Carry impulses from sensory receptors → CNS.
• Cell bodies located in dorsal root ganglia.
• Detect modalities: touch, temperature, pain, etc.
– Motor (Efferent) Neurons
• Carry impulses from CNS → effectors.
• Sub-classes:
▸ Somatic motor neurons – innervate skeletal muscle (voluntary).
▸ Autonomic motor neurons – innervate smooth muscle, cardiac muscle, glands (involuntary).
• Divisions: sympathetic & parasympathetic.
– Interneurons (Association neurons)
• Entirely within CNS; perform integration, information storage & relay.
• Represent > 99\% of all neurons.

• Neuroglia (Supporting Cells): do NOT conduct impulses but enable neural function
• CNS glia
– Astrocytes: most abundant; regulate extracellular K^+, remove NTs, induce/maintain blood-brain barrier (BBB), modulate synapses.
– Oligodendrocytes: myelinate CNS axons; one cell → up to 50 internodes.
– Microglia: immune surveillance; derived from monocytes.
– Ependymal cells: line ventricles & central canal; aid cerebrospinal fluid (CSF) production & circulation.
• PNS glia
– Schwann cells: myelinate PNS axons; one cell = one internode on one axon.
– Satellite cells: envelop neuron somata in ganglia; regulate micro-environment.

Myelin Sheath: Formation & Function

• Definition: multilamellar lipid wrapping → ↓ membrane capacitance, ↑ resistance → rapid conduction via saltatory mechanism.
• PNS myelin
• Formed by Schwann cells wrapping concentrically around a segment of a single axon.
• Nodes of Ranvier: exposed gaps; very high density of voltage-gated Na^+ channels → AP “re-fires” here.
• CNS myelin
• Oligodendrocyte processes wrap multiple axons (≤50).
• Clinical correlations
• Multiple sclerosis (MS): autoimmune destruction of CNS myelin → conduction failure, motor/sensory deficits.
• Guillain-Barré syndrome: immune attack on PNS myelin → ascending weakness.

Blood–Brain Barrier (BBB)

• Purpose: isolates CNS from blood-borne fluctuations & toxins.
• Structure
• Tight junctions between brain capillary endothelial cells.
• Astrocytic end-feet reinforce / signal for junction maintenance.
• Transport across is transcellular, not paracellular.
• Permitted: lipophilic gases (O₂, CO₂), ethanol, nicotine; glucose via GLUT1; selected amino acids.
• Restricted: large proteins, most ions, many pharmacological agents.
• Compromise: infection (meningitis), trauma, ischemia → BBB leak → neuronal risk.

Action Potential (AP) Generation: Step-by-Step

1. Resting membrane potential: \approx -70\;\text{mV} maintained by Na^+/K^+ ATPase (3 Na^+ out / 2 K^+ in) + leak channels.

2. Threshold: \approx -55\;\text{mV}; adequate depolarizing stimulus opens voltage-gated Na^+ channels.

3. Depolarization: rapid Na^+ influx → Vm → +30\;\text{mV}.

4. Repolarization: Na^+ channels inactivate; voltage-gated K^+ channels open → K^+ efflux.

5. Hyperpolarization (after-potential): K^+ channels stay open longer → Vm ≈ -80\;\text{mV}.

6. Return to rest: K^+ channels close; ATPase re-stabilizes gradients.
   • Refractory periods
   • Absolute: while Na^+ channels inactivated → no 2nd AP possible.
   • Relative: during hyperpolarization; stronger stimulus can fire.

AP Characteristics & Conduction Velocity

• All-or-none: crossing threshold ensures full-amplitude AP; stimulus intensity coded by frequency, not size.
• Constant amplitude: non-decremental along axon.
• Directionality: refractory periods enforce forward propagation.

• Unmyelinated axons
• Continuous conduction: each membrane segment sequentially depolarizes; slower.
• Myelinated axons
• Saltatory conduction: AP leaps node→node; myelin prevents ionic leak → velocities up to 120\,\text{m·s}^{-1}.
• Demyelination → slowed/blocked transmission (e.g., MS).

Synapses: Electrical vs. Chemical

• Electrical synapses
• Gap junctions (connexins) → cytoplasmic continuum for ions/small molecules.
• Ultra-fast, bidirectional, synchronous activity; seen in cardiac muscle, some CNS circuits, uterine & visceral smooth muscle.
• Chemical synapses
• Components: presynaptic terminal, synaptic cleft (~20–40 nm), postsynaptic membrane with receptors.
• Sequence:
1. AP arrives at terminal.
2. Voltage-gated Ca^{2+} channels open.
3. Ca^{2+} influx triggers exocytosis of neurotransmitter-filled vesicles.
4. NT diffuses, binds ligand-gated channels (ionotropic) or GPCRs (metabotropic).
5. Termination: reuptake, enzymatic degradation, or diffusion.

Postsynaptic Potentials

• EPSP (excitatory): usually Na^+ or Ca^{2+} influx → depolarization → Vm toward threshold.
• IPSP (inhibitory): K^+ efflux or Cl^- influx → hyperpolarization → Vm away from threshold.
• Graded, not all-or-none; integrate via spatial & temporal summation at axon hillock.

Ligand-Gated (Ionotropic) Channel Example: Nicotinic ACh Receptor

• Location: skeletal neuromuscular junction, some CNS areas.
• Mechanism:

1. ACh binds receptor.

2. Channel opens → Na^+ in, K^+ out (net depolarization).

3. Generates EPSP; if threshold reached → muscle AP & contraction.
   • Fast onset, always excitatory.

G-Protein-Coupled Channel Example: Muscarinic ACh Receptor

• Sites: cardiac muscle, smooth muscle, CNS.
• Mechanism:

1. ACh binds GPCR.

2. G-protein splits; \beta\gamma subunit opens K^+ channels in SA node.

3. K^+ efflux → hyperpolarization → slower HR (vagal tone).
   • Slower onset, longer-lasting, modulatory.

Acetylcholinesterase (AChE)

• Action: hydrolyzes ACh \rightarrow acetate + choline within cleft; choline recycled.
• Significance: prevents sustained depolarization & desensitization.
• Inhibition: organophosphates/nerve gases block AChE → excess ACh → muscle spasm, paralysis, respiratory failure.

Monoamine Neurotransmitters & Inactivation

• Catecholamines: dopamine, norepinephrine (NE), epinephrine (Epi).
• Indolamine: serotonin (5-HT).
• Histamine.
• Termination:

1. Reuptake by specific transporters (primary).

2. Enzymatic degradation:
   – MAO (mitochondrial).
   – COMT (postsynaptic membrane).
   • Clinical: MAO-inhibitors ↑ synaptic monoamines → antidepressant effect.

Dopaminergic Pathways

• Nigrostriatal (substantia nigra → striatum): motor control; degeneration → Parkinson’s disease (resting tremor, rigidity, bradykinesia).
• Mesolimbic / Mesocortical (ventral tegmentum → limbic system & cortex): reward, motivation, emotion; hyperactivity → schizophrenia positive symptoms; D₂ antagonists = antipsychotics.

Major Inhibitory NTs: GABA & Glycine

• GABA: principal brain inhibitor.
• GABAA (ionotropic) → Cl^- influx; GABAB (metabotropic) → K^+ efflux / ↓ Ca^{2+}.
• Glycine: principal spinal cord inhibitor; opens Cl^- channels.
• Tetanus toxin blocks glycine release → unchecked excitation → spastic paralysis.

Additional Neurotransmitter Categories

• Neuropeptides
• Substance P: pain transmission.
• Endorphins / enkephalins: endogenous opioids → analgesia, euphoria.

• Gaseous NTs
• Nitric oxide (NO): diffuses freely, activates guanylyl cyclase (↑ cGMP); retrograde messenger modulating presynaptic release.

• Endocannabinoids
• Bind CB1 GPCRs; retrograde inhibition of NT release; roles in appetite, memory, mood.

Summation & Integration

• Spatial summation: multiple inputs at separate sites simultaneously add.
• Temporal summation: rapid, successive inputs from one synapse accumulate.
• Net EPSP – IPSP balance at axon hillock decides AP initiation.

Synaptic Plasticity: LTP & LTD

• Long-Term Potentiation (LTP): persistent ↑ synaptic strength; classic in hippocampus (learning/memory).
• Requires glutamate binding AMPA & NMDA receptors → Ca^{2+} influx → kinase activation → receptor insertion/synthesis.
• Long-Term Depression (LTD): activity-dependent ↓ strength (low-frequency stimulation); removes weak connections.
• Presynaptic inhibition: axo-axonic synapse ↓ Ca^{2+} entry → ↓ NT release.
• Postsynaptic inhibition: IPSPs hyperpolarize postsynaptic membrane via K^+ or Cl^- channels.