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The Synapse

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Classification 1 - By Transmission Mechanism

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1. Electrical Synapses

• Occur at specialized sites called gap junctions
• The membranes of two cells are separated by only ~3 nm
• Six connexin subunits form a channel called a connexon; two connexons (one from each cell) combine to make a gap junction channel
• Ions pass directly from the cytosol of one cell to the cytosol of the other - no chemical intermediary is needed
• Transmission is bidirectional (unlike chemical synapses)
• Signal propagation is immediate (no delay)
• Found between dendrites, cell bodies, axons, cardiac muscle cells, smooth muscle, glia, and epithelial cells
• Particularly common in early development; help coordinate synchronous neuronal firing (e.g., hypothalamic hormone-secreting neurons)

"Electrical synapses are relatively simple in structure and function, and they allow the direct transfer of ionic current from one cell to the next." - Neuroscience: Exploring the Brain, 5th ed.

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2. Chemical Synapses

• Most synapses in the mature human CNS are chemical
• Pre- and postsynaptic membranes separated by a synaptic cleft of 200-300 Å (20-50 nm) - about 10 times wider than a gap junction
• The cleft is filled with a fibrous extracellular protein matrix that binds the membranes together
• The presynaptic terminal contains:
  • Synaptic vesicles (~50 nm) - store neurotransmitter
  • Large dense-core vesicles / secretory granules (~100 nm) - contain soluble proteins
  • Mitochondria - provide ATP for neurotransmitter synthesis
  • Active zones - the actual sites of neurotransmitter release
• The postsynaptic membrane contains the postsynaptic density (dense accumulation of receptor proteins)
• Transmission is unidirectional (presynaptic → postsynaptic)
• There is a brief synaptic delay compared to electrical synapses
• Signal can be excitatory or inhibitory depending on the neurotransmitter released and the receptor present

1. An action potential arrives at the presynaptic terminal
2. Depolarization opens voltage-gated Ca²⁺ channels
3. Ca²⁺ influx triggers vesicle fusion and exocytosis of neurotransmitter
4. Neurotransmitter diffuses across the cleft and binds to postsynaptic receptors
5. Depending on the receptor type, the postsynaptic cell is either excited or inhibited

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Classification 2 - By Location (Morphological Types)

"The contact site and direction of communication determine the way in which a synapse is named: axodendritic, axosomatic, and axoaxonic synapses." - Medical Physiology

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Classification 3 - By Functional Effect

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Quick Comparison Summary

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Synapse - Complete Classification

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Classification 1 - ANATOMICAL (by location/site of contact)

"Synapses can form on many parts of a neuron, not just from the axon of one neuron to the dendrite of another neuron as axodendritic synapses." - Stahl's Essential Psychopharmacology

• Neuromuscular junction (NMJ) - motor axon → skeletal muscle (one of the largest synapses in the body)
• Neuroeffector junction - autonomic axon → smooth muscle, cardiac muscle, or glands

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Classification 2 - PHYSIOLOGICAL (by effect on postsynaptic membrane)

A. Excitatory Synapse

• Opens Na⁺ channels on the postsynaptic membrane
• Na⁺ influx causes depolarization of the postsynaptic membrane
• Produces an Excitatory Postsynaptic Potential (EPSP)
• EPSP reversal potential ~0 mV (Na⁺ and K⁺ conduct equally through the channel)
• Makes the postsynaptic neuron more likely to fire
• Example neurotransmitters: glutamate, aspartate, acetylcholine

B. Inhibitory Synapse

• Opens Cl⁻ channels (or K⁺ channels) on the postsynaptic membrane
• Cl⁻ influx (or K⁺ efflux) causes hyperpolarization
• Produces an Inhibitory Postsynaptic Potential (IPSP)
• IPSP moves membrane potential toward ~-70 mV (Cl⁻ Nernst potential)
• Makes the postsynaptic neuron less likely to fire
• Example neurotransmitters: GABA, glycine

C. Modulatory Synapse

• Does not directly cause EPSP/IPSP but alters the neuron's response to other inputs
• Works via G-protein coupled receptors (GPCRs) and second messenger cascades
• Example: norepinephrine via β-adrenergic receptors activates cAMP → phosphorylates K⁺ channels → reduces adaptation and increases sustained firing
• Responses last from milliseconds to days
• Example neurotransmitters: norepinephrine, dopamine, serotonin, neuropeptides

"Modulatory transmitters allow the nervous system tremendous potential and flexibility." - Medical Physiology (Boron & Boulpaep)

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Classification 3 - FUNCTIONAL (by mechanism of transmission)

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Classification 4 - CHEMICAL (by neurotransmitter used)

"All skeletal neuromuscular junctions use acetylcholine. In contrast, neuronal synapses use many transmitters. The most ubiquitous are amino acids: glutamate and aspartate excite, whereas GABA and glycine inhibit." - Medical Physiology

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Classification 5 - MORPHOLOGICAL (by ultrastructural appearance under electron microscopy)

• Bouton terminal (end bulb) - the enlarged presynaptic terminal at the axon's endpoint
• Bouton en passant - synaptic contacts made along the course of an axon (not just at the end)
• Synapses are not visible in routine H&E staining; silver staining (Golgi method) is needed to visualize them under light microscopy

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Summary Table - All 5 Classifications

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