A synapse is a specialised site where a neuron communicates with another cell. The target may be another neuron, a skeletal muscle fibre, a cardiac or smooth muscle cell, or a glandular cell. Most synapses in the human nervous system are chemical synapses, where the presynaptic cell releases a neurotransmitter that crosses a narrow extracellular space and binds receptors on the postsynaptic cell.
A typical chemical synapse contains a presynaptic terminal, synaptic vesicles, voltage gated calcium channels, a synaptic cleft and a postsynaptic membrane containing specialised receptors and signalling proteins. Synapses allow information to be transmitted selectively rather than causing every electrically connected cell to respond identically. Their properties also permit amplification, inhibition, modulation and long term changes in connection strength.
Chemical synaptic transmission begins when an action potential reaches the presynaptic terminal. The resulting depolarisation opens voltage gated calcium channels, allowing calcium ions to enter. Calcium binds molecular machinery associated with synaptic vesicles and triggers vesicle fusion with the presynaptic membrane. Neurotransmitter molecules are released by exocytosis into the synaptic cleft and diffuse across it. They bind receptors on the postsynaptic membrane, changing ion conductance or intracellular signalling. The effect may be excitatory, inhibitory or modulatory. Neurotransmitter action is terminated by reuptake, enzymatic breakdown, diffusion or combinations of these mechanisms. The precise sequence occurs on a very small spatial and temporal scale, allowing neural circuits to transmit information rapidly while maintaining strong control over signalling.
Postsynaptic receptors are central to synaptic function. Ionotropic receptors are ligand gated ion channels that open or close directly when a chemical messenger binds. They generally produce rapid postsynaptic responses. Metabotropic receptors, often G protein coupled receptors, influence intracellular pathways and ion channels through intermediary molecular mechanisms. Their effects can be slower and longer lasting and can modify the responsiveness of the neuron to other inputs.
A single neurotransmitter can therefore have different effects at different synapses because receptor subtype, ion permeability and intracellular signalling differ. Synaptic strength is consequently a property of a particular connection rather than a fixed property of a neurotransmitter alone. This receptor diversity greatly expands the computational capabilities of neural circuits.
Synapses can be excitatory or inhibitory depending on their physiological effect. Excitatory postsynaptic potentials generally increase the likelihood that a postsynaptic neuron will reach action potential threshold, whereas inhibitory postsynaptic potentials reduce that likelihood. In many central neurons, glutamate is the principal fast excitatory transmitter and gamma aminobutyric acid is the principal fast inhibitory transmitter, although the effect ultimately depends on receptor and ion gradients. Synaptic inputs are integrated through spatial and temporal summation. A neuron may receive thousands of inputs, and the final response depends on the combined timing and strength of these signals. Inhibitory synapses can act near the cell body or axon initial segment and exert strong control over whether excitatory inputs produce firing.
Electrical synapses are a different type of synapse in which gap junction channels directly connect adjacent cells. Ions can pass between cells without the intermediate release and receptor binding steps characteristic of chemical synapses. Electrical synapses therefore provide very rapid communication and can synchronise populations of neurons. Chemical synapses are more flexible because they can provide strong directionality, amplification, inhibition, neuromodulation and plasticity. The two types are not simply faster and slower versions of the same mechanism. They represent different biological solutions to the problem of coordinating cellular activity. Their distribution varies across neural circuits according to the timing and computational properties required.
Synapses are highly dynamic structures. Their strength can change through short term and long term plasticity. Short term changes can result from alterations in calcium accumulation and vesicle release probability, causing facilitation or depression during repeated activity. Longer lasting changes can involve receptor trafficking, changes in gene expression, structural alterations in dendritic spines and modifications of presynaptic terminals. Long term potentiation and long term depression are extensively studied examples of mechanisms that can alter synaptic efficacy. Such plasticity is important for development, adaptation and learning. Synaptic pruning during development also removes or weakens some connections, helping neural networks become more specialised. The balance between synaptic formation, strengthening, weakening and elimination is therefore central to healthy nervous system function.
Synaptic organisation has important clinical significance. Drugs can alter synaptic transmission by changing neurotransmitter synthesis, release, receptor activation, reuptake or degradation. Many neurological and psychiatric treatments act partly through such mechanisms. Toxins can also disrupt synaptic transmission, sometimes producing paralysis by interfering with neurotransmitter release or receptor function. Diseases affecting synaptic proteins can alter communication and contribute to seizures, movement disorders, cognitive impairment or developmental conditions.
Synapses are also targets of research into neurodegenerative disease because abnormal protein accumulation and impaired synaptic function can precede extensive neuronal loss in some disorders. Their microscopic size does not reduce their importance because the combined behaviour of enormous numbers of synapses determines much of the functional output of neural circuits.
A synapse should not be imagined as a simple permanent gap between two wires. It is a complex molecular structure that controls information transfer with remarkable specificity. Most chemical synapses transmit in one principal direction, from presynaptic to postsynaptic cell, although feedback and retrograde signalling can influence the presynaptic side. Synapses can also be located in different parts of a neuron, including dendrites, the cell body and axon terminals, and location can affect their influence.
Synaptic transmission introduces a delay compared with direct electrical conduction, but that delay is accompanied by enormous flexibility. Synapses allow the nervous system to select, transform, suppress and combine signals, making them fundamental to sensation, movement, learning, memory and the regulation of internal physiological states.
