Synapses – Detailed Study Notes

Chapter 11, Part 3 c focuses on how a single neuron conveys information to another neuron or to an effector cell (skeletal muscle, gland, etc.).
This topic synthesises:
- Neuronal anatomy (soma, axon, dendrites, axon hillock).
- The biophysics of the action potential (AP).
- Graded potentials and synaptic integration.
Clinical and practical importance: understanding synaptic physiology underlies treatment of mood disorders (SSRIs, MAOIs), neuromuscular physiology, and developmental neurobiology.

Axodendritic
- Axon terminals of presynaptic neuron → dendrites of postsynaptic neuron.
- Most prevalent arrangement.
Axosomatic
- Axon terminals → soma (cell body) of target neuron.
- Equally common; often produces larger postsynaptic effects because it is closer to the axon hillock.
Axoaxonic (rare)
- Axon terminal → axon or axon hillock of target neuron.
- Can powerfully modulate neurotransmitter release from the target axon.
Less frequent special cases (mentioned indirectly): synapses onto effector organs (neuromuscular junction, neuroglandular junction).

Synapse – the specialised junction that permits communication between cells.
Presynaptic neuron
- Brings information to the synapse.
- Features: axon terminal branches, synaptic boutons, voltage-gated channels, vesicles.
Postsynaptic neuron (or effector cell)
- Receives information and propagates it away from the synapse.
Synaptic cleft – extracellular space (≈ 20–50 nm wide) filled with interstitial fluid and often a basement membrane; prevents direct cytoplasmic continuity.

Electrical synapses
- Cytoplasmic continuity via gap junctions.
- Ion flow produces direct, rapid signalling.
- Prominent in embryonic nervous tissue and in organs such as the heart; uncommon in mature CNS.
Chemical synapses (focus of nervous system)
- Rely on secretion of neurotransmitter that diffuses across the cleft.
- Provide flexibility, integration, amplification, and inhibition.

Presynaptic bouton (axon terminal)
- Mitochondria (ATP for transport & vesicle cycling).
- Synaptic vesicles loaded with neurotransmitter (NT).
- Voltage-gated $\text{Ca}^{2+}$ channels concentrated in active zones.
- Protein machinery: v-SNAREs (vesicle) + t-SNAREs (target membrane) → mediate vesicle docking & fusion.
Synaptic cleft
- Filled with interstitial fluid; diffusion path for NT.
Postsynaptic membrane
- Integral membrane receptors / ligand-gated channels (chemically-gated); open/close when NT binds.
- Produces graded potentials (EPSPs or IPSPs) by permitting ion flow.

Action potential arrival
- AP propagates along axon via successive opening of voltage-gated $\text{Na}^+$ and $\text{K}^+$ channels.
Depolarisation of bouton
- Membrane potential change opens voltage-gated $\text{Ca}^{2+}$ channels.
Calcium influx
- $\text{Ca}^{2+}$ rushes in down its electro-chemical gradient.
Vesicle fusion / exocytosis
- $\text{Ca}^{2+}$ activates SNARE complex → vesicle membranes fuse with plasma membrane → NT released.
Diffusion across cleft
- NT molecules travel down concentration gradient ~instantaneously (micro-seconds).
Receptor binding
- NT binds to ligand-gated channels on postsynaptic membrane → conformational change opens pore.
Ion flow & graded potential
- Example given: $\text{Na}^+$ influx → depolarising Excitatory Postsynaptic Potential (EPSP).
- Magnitude governed by (a) NT concentration and (b) frequency of NT release.
Integration at axon hillock of postsynaptic neuron
- If summed graded potentials reach threshold $\approx -55\,\text{mV}$ , a new AP is generated → signal continues.

Stopping the postsynaptic effect requires rapid removal or inactivation of NT.

1 – Reuptake into presynaptic bouton
- Membrane transporters reclaim NT for recycling or degradation.
- Pharmacology: SSRIs (e.g., Prozac) selectively block serotonin reuptake → prolong serotonin action.
2 – Enzymatic degradation in cleft
- Membrane-bound or soluble enzymes (e.g., Monoamine Oxidase, Acetylcholinesterase) metabolize NT.
- MAO inhibitors (MAOIs) block this pathway, increasing monoamine NT levels.
3 – Diffusion away from cleft
- NT molecules simply drift out into the surrounding extracellular fluid, diluting their local concentration.
Primary switch
- Ceasing presynaptic APs immediately halts further NT release.

Excitatory (EPSP)
- Usually Na⁺ or Ca²⁺ entry → depolarization.
Inhibitory (IPSP)
- Often Cl^- entry or K⁺ exit → hyperpolarization.
Graded; amplitude $\propto$ number/frequency of open receptors.
Spatial and temporal summation determine whether axon hillock reaches threshold.

The same voltage-gated $\text{Na}^+$ and $\text{K}^+$ channels discussed in AP propagation now trigger synaptic events.
SNARE-mediated exocytosis links cell biology (vesicular transport) with neurophysiology.
Graded potentials reviewed earlier now contextualised as the output of chemical synapses.

Depression & Anxiety: Pharmacological manipulation of reuptake (SSRIs) or enzymatic breakdown (MAOIs) alters synaptic signalling.
Neuromuscular blockers target synaptic transmission at the neuromuscular junction.
Neurotoxins (botulinum, tetanus) interfere with SNARE-mediated vesicle fusion.
Developmental neurobiology: electrical synapses more prominent prenatally, later replaced by chemical synapses for flexibility.

Modifying synaptic chemistry (e.g., antidepressants) raises questions about identity, mood regulation, and long-term neural plasticity.
Understanding synaptic dynamics informs debates on neural enhancement and treatment vs. augmentation.

AP in presynaptic axon → 2. $\text{Ca}^{2+}$ influx → 3. Vesicle fusion → 4. NT release → 5. Diffusion across cleft → 6. Receptor binding → 7. Ion flow → 8. Graded potential (EPSP/IPSP) → 9. Threshold reached? If yes → new AP; if no → signal dissipates.
Termination via reuptake, degradation, or diffusion.

End of comprehensive study notes on synapses.