Illustration of the major elements in chemical synaptic transmission. An electrochemical wave called an action potential travels along the axon of aneuron. When the action potential reaches a synapse, it provokes the release of a small quantity of neurotransmitter molecules, which bind to chemical receptor molecules located in the membrane of another neuron, on the opposite side of the synapse.

Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles orglands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie perception and thought. They allow the nervous system to connect to and control other systems of the body.

At a chemical synapse, one neuron releases neurotransmitter molecules into a small space (the synapse) that is adjacent to another neuron. These molecules then bind to the neuroreceptors on the receiving cell's side of the synaptic cleft. Finally, the neurotransmitters must be cleared out of the synapse efficiently so that the synapse can be ready to function again as soon as possible.

The adult human brain is estimated to contain from 10¹⁴ to 5 × 10¹⁴ (100–500 trillion) synapses.^[1] Every cubic millimeter of cerebral cortex contains roughly a billion of them.^[2]

The word "synapse" comes from "synaptein", which Sir Charles Scott Sherrington and colleagues coined from the Greek "syn-" ("together") and "haptein" ("to clasp"). Chemical synapses are not the only type of biological synapse: electrical and immunological synapses also exist. Without a qualifier, however, "synapse" commonly means chemical synapse.

For more details on formation of synapses, see Synaptogenesis.

Synapses are functional connections between neurons, or between neurons and other types of cells.^[3][4] A typical neuron gives rise to several thousand synapses, although there are some types that make far fewer.^[5] Most synapses connect axons to dendrites,^[6][7] but there are also other types of connections, including axon-to-cell-body,^[8][9] axon-to-axon,^[8][9] and dendrite-to-dendrite.^[7] Synapses are generally too small to be recognizable using a light microscope except as points where the membranes of two cells appear to touch, but their cellular elements can be visualized clearly using an electron microscope.

Chemical synapses pass information directionally from a presynaptic cell to a postsynaptic cell and are therefore asymmetric in structure and function. The presynaptic terminal, or synaptic bouton, is a specialized area within the axon of the presynaptic cell that contains neurotransmittersenclosed in small membrane-bound spheres called synaptic vesicles. Synaptic vesicles are docked at the presynaptic plasma membrane at regions called active zones.

Immediately opposite is a region of the postsynaptic cell containing neurotransmitter receptors; for synapses between two neurons the postsynaptic region may be found on the dendrites or cell body. Immediately behind the postsynaptic membrane is an elaborate complex of interlinked proteins called the postsynaptic density (PSD).

Proteins in the PSD are involved in anchoring and trafficking neurotransmitter receptors and modulating the activity of these receptors. The receptors and PSDs are often found in specialized protrusions from the main dendritic shaft called dendritic spines.

Synapses may be described as symmetric or asymmetric. When examined under an electron microscope, asymmetric synapses are characterized by rounded vesicles in the presynaptic cell, and a prominent postsynaptic density. Asymmetric synapses are typically excitatory. Symmetric synapses in contrast have flattened or elongated vesicles, and do not contain a prominent postsynaptic density. Symmetric synapses are typically inhibitory.

Between the pre- and postsynaptic cells is a gap about 20 nm wide called the synaptic cleft. The small volume of the cleft allows neurotransmitter concentration to be raised and lowered rapidly.^[10]

Signaling in chemical synapses Overview

Here is a summary of the sequence of events that take place in synaptic transmission from a presynaptic neuron to a postsynaptic cell. Each step is explained in more detail below. Note that with the exception of the final step, the entire process may run only a few tenths of a millisecond, in the fastest synapses.

1. The process begins with a wave of electrochemical excitation called an action potential traveling along the membrane of the presynaptic cell, until it reaches the synapse.

2. The electrical depolarization of the membrane at the synapse causes channels to open that are permeable to calcium ions.

3. Calcium ions flow through the presynaptic membrane, rapidly increasing the calcium concentration in the interior.

4. The high calcium concentration activates a set of calcium-sensitive proteins attached to vesicles that contain a neurotransmitter chemical.

5. These proteins change shape, causing the membranes of some "docked" vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter contents into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells.

6. The neurotransmitter diffuses within the cleft. Some of it escapes, but some of it binds to chemical receptor molecules located on the membrane of the postsynaptic cell.

7. The binding of neurotransmitter causes the receptor molecule to be activated in some way. Several types of activation are possible, as described in more detail below. In any case, this is the key step by which the synaptic process affects the behavior of the postsynaptic cell.

8. Due to thermal shaking, neurotransmitter molecules eventually break loose from the receptors and drift away.

9. The neurotransmitter is either reabsorbed by the presynaptic cell, and then repackaged for future release, or else it is broken down metabolically.

Neurotransmitter release

The release of a neurotransmitter is triggered by the arrival of a nerve impulse (or action potential) and occurs through an unusually rapid process of cellular secretion (exocytosis). Within the presynaptic nerve terminal, vesicles containing neurotransmitter are localized near the synaptic membrane. The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels at the down stroke of the action potential (tail current).^[11] Calcium ions then bind with the proteins found within the membranes of the synaptic vesicles, allowing the vesicles to fuse with the presynaptic membrane, resulting in the creation of a fusion pore. The vesicles then release their contents to the synaptic cleft through this fusion pore^[12] within 180 µsec of calcium entry.^[11] Vesicle fusion is driven by the action of a set of proteins in the presynaptic terminal known asSNAREs. As a whole, the protein complex or structure that mediates the docking and fusion of presynaptic vesicles is called the active zone.^[13] The membrane added by this fusion is later retrieved by endocytosis and recycled for the formation of fresh neurotransmitter-filled vesicles.