Neuronal Propagation, Conduction Velocity, and Synaptic Transmission

Conduction velocity (CV)
- A rate: the distance an action potential (AP) travels per unit time.
- Usually expressed in \text{m·s}^{-1}.
- Formula (conceptual): $v = \frac{\text{distance}}{\text{time}}$ .
Propagation
- Serial opening of voltage-gated Na⁺ channels (VGSCs) along an axon.
- Analogy: dominoes falling one after another.
- Each channel opening ≈ one AP; therefore an axon contains many APs in sequence, not a single travelling "spike".
Key distinction
- CV just quantifies how fast propagation occurs.
- Propagation = mechanism; CV = measurement of that mechanism.

Receptive regions (dendrites, soma)
- Contain ligand-gated or mechanically-gated channels (LG/MechG).
- Also contain leakage channels for Na⁺ & K⁺.
- Na⁺/K⁺-ATPase (pump) ubiquitously active, quickly restores $V_m$ toward $-70\,\text{mV}$ .
- Produce graded potentials (GPs).
- Small, decremental, localized.
- Washed out rapidly by leakage + pump –> little/no propagation here.
Axon (conductive region)
- High density of VGSCs plus VG K⁺ channels.
- Same leakage channels & pumps between VG clusters.
- Capable of regenerative APs and propagation.

Unmyelinated axon
- VGSCs spaced closely; every segment must depolarize.
- Slowest step = Na⁺ influx at each node ("bucket hand-off" in fire-brigade analogy).
Myelinated axon
- Myelin = electrical insulator; no channels under the wrap.
- Channels clustered at nodes of Ranvier only.
- Larger inter-nodal distances –> fewer channel openings –> faster CV.
- Process called saltatory conduction (“jumping” node-to-node).
Fire-brigade analogy
- Oompa-Loompas (short reach) = many hand-offs (slow).
- Tall athletes (long reach) = fewer hand-offs (fast). Myelin functions like the athletes.
Clinical tie-in: Multiple Sclerosis (MS)
- Autoimmune loss of oligodendrocytes –> demyelination.
- Initially slows/blocks APs; neurons add new VGSCs to compensate (slower CV).
- Recurrent cycles cause progressive motor/sensory deficits; possible pain component.

Group (α) A fibers
- Largest diameter (up to $20\,\mu\text{m}$ ) + myelinated.
- CV up to 150\,\text{m·s}^{-1}.
- Equivalent to Roman-numeral Type I.
Group B fibers
- Intermediate diameter, "lightly myelinated" (fewer wraps or large nodes).
- Autonomic pre-ganglionic fibers.
Group C fibers
- Smallest diameter, unmyelinated.
- Autonomic post-ganglionic + slow pain (dull, aching) afferents.
- Slowest CV (≈ 0.5–2\,\text{m·s}^{-1}).

Chemical synapse components
- Presynaptic axon terminal (bouton) – contains vesicles w/ neurotransmitter (NT).
- Synaptic cleft (≈ 20–40 nm) – filled with interstitial fluid & basement membrane fragments.
- Postsynaptic membrane – dense with ligand-gated receptors (LGICs).
Common anatomical subtypes
- Axodendritic (most common).
- Axosomatic (2nd most common).
- Axo-axonic (rare; modulatory).
Pre- vs Post-synaptic
- “Pre” carries information toward the cleft; “Post” receives.
- Gap junction synapses exist embryonically but are rare in adult CNS (common in cardiac tissue).

AP arrives at bouton –> depolarization.
Depolarization opens voltage-gated Ca²⁺ channels (VGCCs).
Ca²⁺ influx (charge $+2$ ) triggers vesicle docking (v-SNARE ↔ t-SNARE).
Exocytosis releases NT into cleft.
NT diffuses across cleft and binds postsynaptic LGICs.
LGICs open – ion flow generates a postsynaptic graded potential.
- Magnitude ∝ amount of NT (more Ca²⁺ influx → more vesicles → larger GP).
NT cleared by
- Enzymatic degradation (e.g.
  - Acetylcholinesterase (AChE) for acetylcholine).
- Re-uptake into presynaptic terminal (e.g.
  - Serotonin transporter – target of SSRIs like Prozac).
- Diffusion away (perfusion into nearby ISF/blood).

Excitatory postsynaptic potential (EPSP)
- Depolarizing graded potential.
- Typically Na⁺ influx (occasionally mixed Na⁺/Ca²⁺).
Inhibitory postsynaptic potential (IPSP)
- Hyperpolarizing graded potential.
- Usually K⁺ efflux or Cl⁻ influx.
Key rule set
- Na⁺ → EPSP.
- K⁺ or Cl⁻ → IPSP.
- Ca²⁺ at synapse = vesicle release trigger, not direct PSP (except in some specialized receptors).

Temporal summation
- One presynaptic neuron fires multiple APs in rapid succession.
- Second GP starts before the first fully decays –> additive $\Delta V_m$ .
Spatial summation
- ≥2 different presynaptic neurons fire simultaneously onto distinct postsynaptic sites.
- GPs converge and algebraically sum.
- Can involve:
- EPSP + EPSP (enhanced depolarization).
- IPSP + IPSP (enhanced hyperpolarization).
- EPSP + IPSP (mutual cancellation if equal magnitude).
Threshold concept
- Summed postsynaptic potentials must reach axon hillock threshold (≈ $-55\,\text{mV}$ ) to trigger axonal AP.

Skeletal muscle vs neuron
- Muscle end-plate has VGSCs immediately adjacent to nicotinic ACh receptors; neuronal dendrites do not.
- Neuronal GPs must travel (electrotonically) to the axon hillock before AP initiation.
Drug & disease relevance
- AChE inhibitors (nerve agents, myasthenia gravis Tx) prolong ACh action.
- SSRIs enhance serotonergic EPSPs by blocking reuptake.
- Demyelinating diseases (MS, Guillain-Barré) decrease CV, produce functional deficits.
Physiological implications
- Fast CV crucial for reflex arcs, proprioception, and motor control.
- Slow CV fibers suited for modulatory or lingering sensations (e.g., chronic pain).

$v = \frac{d}{t}$ (definition of conduction velocity).
Typical thresholds & potentials
- Resting $V_m \approx -70\,\text{mV}$ .
- Threshold $V_{th} \approx -55\,\text{mV}$ .
Ionic equilibrium potentials (approx.)
- $E_{Na} \approx +60\,\text{mV}$
- $E_{K} \approx -90\,\text{mV}$
- $E_{Cl} \approx -70\,\text{mV}$ (tends to stabilize/hyperpolarize).

Understanding of AP propagation underlies modern therapies (nerve grafts, demyelination treatments, neuropharmacology).
Highlights evolutionary trade-offs: larger axons & myelination demand metabolic and spatial costs but yield faster information transfer.
Demonstrates the principle that "speed of communication" is not uniformly necessary—organisms optimize CV according to functional need (e.g., fast escape reflex vs slow visceral control).