Neuronal Signaling & Synaptic Transmission – Comprehensive Study Notes

Neuron Anatomy & Signal Direction

• Cellular Components
  • Dendrites: Receive incoming information; high surface area for synaptic inputs.
  • Cell body (soma): Integrates signals; contains nucleus & organelles.
  • Axon hillock: Decision point where graded potentials are converted to an action potential (AP) if threshold is reached.
  • Axon: Conducts APs away from soma toward terminals.
  • Presynaptic terminal (axon terminal): Releases neurotransmitter (NT) or forms a gap junction.
  • Synapse: Specialized junction; information flows pre- → post- synaptic cell.
  • Chemical synapse (most common).
  • Electrical synapse (gap-junction–mediated coupling).

Types of Synapses

• Chemical Synapse
  • AP arrives → voltage-gated $Ca^{2+}$ channels open → $Ca^{2+}$ influx.
  • Synaptic vesicles fuse with presynaptic membrane; NT released into cleft.
  • NT binds:
  • Ionotropic receptor (ligand-gated ion channel) → rapid EPSP/IPSP.
  • Metabotropic receptor (GPCR) → slower biochemical cascades, gene expression changes.
  • Signal termination
  • Enzymatic breakdown in cleft (e.g., acetylcholinesterase).
  • Re-uptake into presynaptic neuron.
• Electrical Synapse
  • Gap-junction channels directly couple cytosol of adjacent cells.
  • Ions & small molecules flow bidirectionally; almost instantaneous signal (coupling potential).

Ion Concentrations (Mammalian Neuron)

• Inside vs. outside establish electrochemical gradients driving APs:
  • $[K^+]<em>{in} = 140\,\text{mM}$, $[K^+]</em>{out} = 5\,\text{mM}$ (high inside).
  • $[Na^+]<em>{in} = 15\,\text{mM}$, $[Na^+]</em>{out} = 150\,\text{mM}$ (high outside).
  • $[Cl^-]<em>{in} = 10\,\text{mM}$, $[Cl^-]</em>{out} = 120\,\text{mM}$.
  • Large anionic proteins $A^-$ predominantly inside (~$100\,\text{mM}$).

Membrane Channels & Transporters

• Non-gated (leak) channels: Always open; maintain resting potential.
• Gated Channels
  • Voltage-gated (respond to Vm changes).
  • Ligand-gated (extracellular NT or intracellular messenger).
  • Stress-activated (mechanical stretch).
• Sodium–Potassium Pump (Na⁺/K⁺-ATPase)
  • Electrogenic antiporter: $3\,Na^+<em>{out} / 2\,K^+</em>{in}$ per ATP.
  • Restores ionic gradients post-AP; active during refractory period.

Electrical Events of an Action Potential

• Resting Potential
  • Vm ≈ $-70\,\text{mV}$ (inside negative).
  • Dominated by $K^+$ leak and $Na^+/K^+$ pump.
• Depolarization (Phase 0)
  • Stimulus opens voltage-gated $Na^+$ channels.
  • Rapid $Na^+$ influx → Vm rises to ≈ $+30\,\text{mV}$.
• Repolarization (Phase 1–2)
  • $Na^+$ channels inactivate; voltage-gated $K^+$ channels open.
  • $K^+$ efflux drives Vm back negative.
• Hyperpolarization (After-potential)
  • Excess $K^+$ efflux overshoots to ≈ $-80\,\text{mV}$.
• Refractory Periods
  • Absolute: $Na^+$ channels inactivated; no AP possible.
  • Relative: Vm near hyperpolarized; stronger stimulus required.

Graded Potentials

• Hyperpolarizing events: Increased $K^+$ permeability → Vm more negative.
• Depolarizing events: Increased $Na^+$ permeability → Vm less negative.
• Graded amplitude (proportional to stimulus); decay with distance/time.
• AP is triggered only if depolarization reaches threshold (≈ $-50\,\text{mV}$).

Propagation of the Action Potential

• Continuous Conduction (unmyelinated axons)
  • Sequential depolarization of every membrane patch; slower.
• Saltatory Conduction (myelinated axons)
  • AP leaps node-to-node (Nodes of Ranvier) where $Na^+$ channels cluster.
  • Myelin (Schwann cell/oligodendrocyte) insulates internodes → faster, energy-efficient.

Postsynaptic Integration

• Summation
  • Subthreshold: Single EPSP below threshold → no AP.
  • Temporal summation: Rapid, successive EPSPs from same synapse add.
  • Spatial summation: EPSPs from multiple synapses combine.
  • EPSP + IPSP interplay: Inhibitory input can cancel excitatory drive.

Neurotransmitter Clearance Mechanisms (Chemical Synapse)

1. Enzymatic degradation (e.g., acetylcholine by AChE).
2. Reuptake transporters (recycle NT into presynaptic terminal).

Major Neurotransmitter Classes (Table 48.2)

• Acetylcholine (ACh)
  • Structure: $HO{-}CH<em>2{-}CH</em>2{-}N^{+}(CH<em>3)</em>3$ (quaternary amine).
• Amino Acids
  • Glutamate ($HO<em>2C{-}CH</em>2{-}CH<em>2{-}CH(NH</em>2){-}COOH$) – primary excitatory NT.
  • $\gamma$-Aminobutyric Acid (GABA): $H<em>2N{-}CH</em>2{-}CH<em>2{-}CH</em>2{-}COOH$ – main CNS inhibitory NT.
  • Glycine: $H<em>2N{-}CH</em>2{-}COOH$ – spinal cord inhibition.
• Biogenic Amines
  • Norepinephrine (NE) – alertness, autonomic.
  • Dopamine – reward, motor control.
  • Serotonin (5-HT) – mood, sleep.
• Neuropeptides (examples)
  • Substance P: $\text{Arg–Pro–Lys–Pro–Gln–Gln–Phe–Phe–Gly–Leu–Met}$ – pain signaling.
  • Met-enkephalin (endorphin): $\text{Tyr–Gly–Gly–Phe–Met}$ – analgesic.
• Gaseous NTs
  • Nitric Oxide (NO): $N = O$ – retrograde signaling, vasodilation.

Functional & Clinical Relevance

• AP conduction enables rapid, long-distance communication fundamental to reflexes, cognition, and behavior.
• Synaptic modulation underlies learning & memory (plasticity) and is targeted by pharmacotherapies (e.g., SSRIs, antiepileptics).
• Myelin integrity is critical; demyelinating diseases (e.g., Multiple Sclerosis) slow saltatory conduction.
• Neurotransmitter imbalance is implicated in psychiatric and neurodegenerative disorders.

Key Terms

• EPSP: Excitatory postsynaptic potential.
• IPSP: Inhibitory postsynaptic potential.
• Ionotropic vs. Metabotropic receptor.
• Threshold, refractory period, gap junction, node of Ranvier.
• Depolarization, repolarization, hyperpolarization.