Why can a synapse only be seen clearly with electron microscopy?

The synaptic cleft and membrane specializations are on the order of tens of nanometers, far below the resolution of the light microscope, so the vesicles, cleft, and postsynaptic density are resolved only by electron microscopy.

How are excitatory and inhibitory synapses told apart structurally?

Excitatory synapses are typically asymmetric (Gray type I) with a thick postsynaptic density, while inhibitory synapses are typically symmetric (Gray type II) with pre- and postsynaptic densities of similar thickness.

Synaptic Structure and Ultrastructure

A synapse is the specialized junction at which a neuron communicates with a target cell. The chemical synapse, the dominant type in the mammalian brain, is defined ultrastructurally by a presynaptic terminal filled with neurotransmitter-containing vesicles, a narrow synaptic cleft, and a postsynaptic membrane thickened by the postsynaptic density. These features, visible only by electron microscopy, are the structural basis of neurotransmission.

Definition

A synapse is a specialized intercellular junction at which a presynaptic neuron transmits a signal to a postsynaptic cell; at a chemical synapse, ultrastructure comprises a vesicle-filled presynaptic terminal, a synaptic cleft, and a postsynaptic density.

Scope

This topic covers the fine structure of synapses as seen by electron microscopy: the presynaptic active zone and synaptic vesicles, the synaptic cleft, the postsynaptic density, and the morphological distinction of excitatory and inhibitory synapses (asymmetric versus symmetric). It also notes the relationship between vesicle docking and neurotransmitter release. It is a reference-educational entry, not clinical guidance.

Core questions

What ultrastructural features define a chemical synapse on electron microscopy?
What is the postsynaptic density and what does it contain?
How are excitatory and inhibitory synapses distinguished morphologically?
How does presynaptic ultrastructure relate to neurotransmitter release?

Key concepts

Chemical synapse
Presynaptic terminal and active zone
Synaptic vesicles
Synaptic cleft
Postsynaptic density
Asymmetric (excitatory, Gray type I) and symmetric (inhibitory, Gray type II) synapses
Electrical synapse (gap junction)

Mechanisms

At a chemical synapse the presynaptic terminal contains clusters of synaptic vesicles docked at the active zone; depolarization triggers calcium-dependent fusion of vesicles with the presynaptic membrane and release of neurotransmitter into the synaptic cleft, where it diffuses to receptors on the postsynaptic membrane (Südhof, 2013). The postsynaptic membrane is marked by an electron-dense postsynaptic density containing receptors and scaffolding proteins. As Harris and Weinberg (2012) describe, excitatory synapses tend to be asymmetric with a prominent postsynaptic density (Gray type I) and inhibitory synapses tend to be symmetric (Gray type II). Less common electrical synapses transmit current directly through gap junctions.

Clinical relevance

Synaptic structure underlies how synaptic loss and dysfunction are studied in neurodegenerative and psychiatric disease and how many neuroactive drugs and toxins act at the synaptic cleft. This entry describes normal ultrastructure for educational reference and does not provide diagnostic or therapeutic recommendations.

History

Sherrington introduced the term synapse around 1897 to name the functional junction between neurons inferred from physiology. Its physical reality was confirmed in the 1950s when electron microscopy resolved the cleft, vesicles, and membrane specializations, and George Gray's classification of asymmetric and symmetric synapses linked ultrastructure to function. Subsequent molecular work, including Südhof's analysis of vesicle fusion, connected this structure to the mechanism of transmitter release.

Key figures

Charles Sherrington
Bernard Katz
George Gray
Thomas Südhof

Seminal works

harris-2012
sudhof-2013

Frequently asked questions

Why can a synapse only be seen clearly with electron microscopy?: The synaptic cleft and membrane specializations are on the order of tens of nanometers, far below the resolution of the light microscope, so the vesicles, cleft, and postsynaptic density are resolved only by electron microscopy.
How are excitatory and inhibitory synapses told apart structurally?: Excitatory synapses are typically asymmetric (Gray type I) with a thick postsynaptic density, while inhibitory synapses are typically symmetric (Gray type II) with pre- and postsynaptic densities of similar thickness.