Chapter 8 Notes – Synaptic Transmission & Neural Integration

Big-Picture Functions of the Nervous System

• Only three core jobs, whether at the scale of one neuron or the whole brain:
  • Sensory – receive information.
  • Integration – digest/interpret the information.
  • Motor – send a decision (neurotransmitter release = a motor act for the neuron).
• A single neuron can perform all three, making the nervous system unique among organ systems.

Chapter 7 Recap (What We Are Building On)

• Electrical events confined to one neuron:
  • Dendrite / soma → graded potentials (EPSPs, IPSPs).
  • Axon hillock → action potential (AP) initiation.
  • Axon → AP propagation.
  • Axon terminal → neurotransmitter (NT) release.

Definition: Synaptic Transmission

• Begins the moment NTs diffuse across the synaptic cleft and bind receptors on another cell.
• Requires ≥ 2 neurons (presynaptic + postsynaptic).
• Leads to neural integration (the “thought” stage at systems level).

Structural Anatomy of a Synapse

• Presynaptic element = axon terminal containing synaptic vesicles.
• Synaptic cleft ≈ microscopic gap.
• Postsynaptic membrane = dendrite or soma (NOT the axon hillock).
• Key proteins
  • Voltage-sensitive $Ca^{2+}$ channels on presynaptic side.
  • Transmembrane receptor proteins on postsynaptic side (ionotropic or metabotropic).

Types of Synapses

• Electrical Synapse
  • Gap junctions = permanent pores → direct ionic current.
  • Pros: near-instantaneous; Cons: no directionality, rare.
• Chemical Synapse
  • Directional, slower (NT must diffuse).
  • Steps
  1. AP depolarises terminal.
  2. $Ca^{2+}$ influx via voltage-sensitive channel.
  3. Vesicle fusion → NT exocytosis.
  4. NT diffusion + receptor binding.

Fast vs. Slow Signal-Transduction Pathways

• Fast (Ionotropic) – “channel-linked”
  • Receptor itself is an ion channel; opens within milliseconds.
  • Two channel flavors:
  • Cation: influx $Na^+, Ca^{2+}$ + efflux $K^+$ (all through SAME pore).
  • Anion: influx only $Cl^-$.
• Slow (Metabotropic) – G-Protein-Coupled
  • Receptor has no pore; activates a trimeric G-protein (α, β, γ).
  • Two sub-categories:
  • Direct coupling – Gα directly opens/closes a separate ion channel.
  • Indirect (second-messenger) coupling – Gα activates an enzyme (e.g., adenylyl cyclase → $cAMP$) which then modulates channels or other targets.
  • Time-scale: seconds → hours; responses can be sustained.

Generating Excitatory Post-Synaptic Potentials (EPSPs)

• Method 1 (Fast) – Open ligand-gated cation channel.
  • NTs: Acetylcholine (ACh), ATP, Glutamate, Serotonin.
  • Net influx of positive charge → local depolarisation.
• Method 2 (Slow) – Close a $K^+$ channel via $cAMP$ cascade.
  • Gα → adenylyl cyclase → $cAMP$ → Protein Kinase A → phosphorylates & shuts $K^+$ leak channel.
  • Prevents $K^+$ efflux → internal positive charge accumulates → depolarisation.
• EPSP magnitude decays with distance; many must summate to influence axon hillock.

Generating Inhibitory Post-Synaptic Potentials (IPSPs)

• Method 1 (Fast) – Open ligand-gated $Cl^-$ channel.
  • NTs: GABA (brain), Glycine (spinal cord).
  • $Cl^-$ influx → inside becomes more negative → hyperpolarisation.
• Method 2 (Fast) – Open ligand-gated $K^+$ channel (efflux only).
  • $K^+$ leaves → loss of positive charge → hyperpolarisation.
• Result: membrane potential driven farther from threshold (e.g., $V_m \rightarrow -90\,\text{mV}$).

Neural Integration at the Axon Hillock

• Axon hillock sums all EPSPs & IPSPs in space and time.
• AP fires if $V_m \geq -55\,\text{mV}$ (threshold).
• Temporal summation – repeated input from ONE presynaptic neuron close in time.
• Spatial summation – simultaneous inputs from MULTIPLE presynaptic neurons at different sites.
• Reality = mix of both; integration decides YES (AP) vs NO.

Frequency Coding (Preview)

• Information is encoded in rate of APs, not their size (all APs are identical).
  • Example: 5 AP s⁻¹ vs 20 AP s⁻¹ carry different meanings.

Presynaptic Modulation (Axo-Axonic Synapses)

• A third neuron contacts the axon terminal of a presynaptic cell.
• Presynaptic Facilitation
  • Example neuron E → terminal C.
  • Increases $Ca^{2+}$ influx → more NT release → larger PSPs in postsynaptic neuron X.
• Presynaptic Inhibition
  • Example neuron H → terminal F.
  • Decreases NT release → smaller PSPs in postsynaptic neuron Y.

Termination of Neurotransmitter Action

1. Enzymatic Degradation
   • ACh + ACh-esterase → acetic acid + choline (choline recycled).
2. Presynaptic Re-uptake
   • Classic for Serotonin; SSRIs (e.g., Prozac) block re-uptake to elevate mood.
3. Spill-over & Glial Uptake
   • NT diffuses out of cleft; neuroglia mop it up.

Key Numerical & Chemical Facts

• Resting $V_m \approx -70\,\text{mV}$.
• Threshold at axon hillock $\approx -55\,\text{mV}$.
• Depolarising EPSP may reach $+20\,\text{mV}$ locally (dendrite) but decays en route.
• Electrical synapse = fastest; chemical synapse adds diffusion delay.
• Ionotropic response latency: milliseconds; Metabotropic: seconds → hours.
• Voltage-sensitive channel specificity
  • $Na^+$ only; $K^+$ only; $Ca^{2+}$ only.
• Ligand-gated cation channel: $Na^+, Ca^{2+}$ in / $K^+$ out simultaneously.
• Ligand-gated anion channel: $Cl^-$ in only.

Common Exam Flags

• Four NTs that open cation channels → EPSP: ACh, ATP, Glutamate, Serotonin.
• Two NTs that open anion channels → IPSP: GABA, Glycine.
• Two mechanisms each for EPSP & IPSP generation.
• Difference between ionotropic vs metabotropic response speed & structure.
• Axo-axonic = presynaptic modulation (facilitation vs inhibition).