Synapse

Synapses are specialized junctions through which cells of the nervous system signal to one another and to non-neuronal cells such as muscles or glands. Synapses define the circuits in which the neurons of the central nervous system interconnect. They are thus crucial to the biological computations that underlie perception and thought. They also provide the means through which the nervous system connects to and controls the other systems of the body.

Table of contents 1 Anatomy and Structure 2 Signalling across the Synapse 3 Synaptic strength 4 Integration of synaptic inputs 5 Detailed properties and regulation

Anatomy and Structure

At a classical synapse, a mushroom-shaped bud projects from each of two cells and the caps of these buds press flat against one another. At this interface, the membranes of the two cells flank each other across a slender gap, the narrowness of which enables signaling molecules known as neurotransmitters to pass rapidly from one cell to the other by diffusion. This gap is sometimes called the synaptic cleft.

Synapses are asymmetric both in structure and in how they operate. Only the so-called pre-synaptic neuron secretes the neurotransmitter, which binds to receptors facing into the synapse from the post-synaptic cell. The pre-synaptic nerve terminal generally buds from the tip of an axon, while the post-synaptic target surface typically appears on a dendrite, a cell body or another part of a cell.

Signalling across the Synapse

The release of neurotransmitter is triggered by the arrival of a nerve impulse (or action potential) and occurs through an unusually rapid process of cellular secretion: Within the pre-synaptic nerve terminal, vesicles containing neurotransmitter sit "docked" and ready at the synaptic membrane. The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels, at which point the vesicles fuse with the membrane and release their contents to the outside. Receptors on the opposite side of the synaptic gap bind neurotransmitter molecules and respond by opening nearby ion channels in the post-synaptic cell membrane, causing ions to rush in or out and changing the local transmembrane potential of the cell. The result is excitatory, in the case of depolarizing currents, or inhibitory in the case of hyperpolarizing currents. Whether a synapse is excitatory or inhibitory depends on what type(s) of ion channel conduct the post-synaptic current, which in turn is a function of the type of receptors and neurotransmitter employed at the synapse.

Synaptic strength

The amount of current, or more strictly the change in transmembrane potential, depends on the "strength" of the synapse, which is subject to biological regulation. One regulatory mechanism involves the simple coincidence of action potentials in the synaptically linked cells. Because the coincidence of sensory stimuli (the sound of a bell and the smell of meat, for example, in the experiments by Pavlov) can give rise to associative learning or conditioning, neuroscientists have hypothesized that synaptic strengthening through coincident activity in two neurons might underlie learning and memory. This is known as the Hebbian theory.

Integration of synaptic inputs

Generally, if an excitatory synapse is strong, an action potential in the pre-synaptic neuron will trigger another in the post-synaptic cell; whereas at a weak synapse the excitatory post-synaptic potential ("EPSP") will not reach the threshold for action potential initiation. In the brain, however, each neuron typically connects or "synapses" to many others, and likewise each receives synaptic "inputs" from many others. When action potentials "fire" simultaneously in several neurons that weakly synapse on a single cell, they may initiate an impulse in that cell even though the synapses are weak. In this way the output of a neuron may depend on the input of many others, each of which may have a different degree of influence, depending on the strength of its synapse with that neuron. Complex input/output relationships form the basis of transistor-based computations in computers, and so are thought to figure similarly in neural circuits.

Detailed properties and regulation

Following fusion of the synaptic vesicles and release of transmitter molecules into the synaptic cleft, the neurotransmitter is rapidly cleared from the space for recycling by specialized membrane proteins in the post-synaptic membrane. This "re-uptake" prevents "desensitization" of the post-synaptic receptors and ensures that succeeding action potentials will elicit the same size EPSP. The necessity of re-uptake and the phenomenon of desensitization in receptors and ion channels means that the strength of a synapse may in effect diminish as a train of action potentials arrive in rapid succession--a phenomenon that gives rise to the so-called frequency dependence of synapses. The nervous system exploits this property for computational purposes, and apparently tunes its synapses through such means as phosphorylation of the proteins involved. The size, number and replenishment rate of vesicles also are subject to regulation, as are many other elements of synaptic transmission. The drugs known as selective serotonin re-uptake inhibitors or SSRIs affect certain synapses by inhibiting the re-uptake of of the neurotransmitter serotonin.

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By analogy to true synapses described above, the interface between an antigen presenting cell and lymphocyte is sometimes called an immunological synapse.