SYNAPSE, BRAIN

The term synapse is from the Greek word synaptein, for "juncture" or "fasten together," by way of the Latin synapsis. It refers to the specialized junction found between nerve cells. It was conceived by the British pioneer neurophysiologist Sir Charles Sherrington (1857-1952) to describe the then-novel microscopic observations that the "end-feet" of one neuron physically contacted, in an intimate manner, other Neurons to which it was structurally connected. A similar point of connection between peripheral nerves and their targets is usually referred to as a junction.

Synapses in the brain (see Figures 1 and 2) are morphologically typed by several features (1) a dilation of the presynaptic terminal (nerve ending) that contains accumulations of synaptic vesicles in various sizes, shapes, and chemical reactivities; (2) mitochondria; (3) a specialized zone of modified thickness and electron opacity in the presynaptic membrane, in which a presynaptic grid is perforated to provide maximum access of transmitter-containing vesicles to the presumptive sites of transmitter release; and (4) a specialized zone of altered thickness and opacity in the postsynaptic membrane termed the active zone and believed to be the site of initial response.

The synaptic vesicles have been shown to contain the Neurotransmitters by a series of extensive analyses of meticuously purified vesicles. The vesicles differ in their protein content and may include the transmitter's synthetic enzymes, as well as the transporters that can concentrate the transmitter within the vesicles. For Monoamine neurons, the vesicles also contain specific proteins (named for their sites of discovery in the adrenal medulla as chromogranins but now termed more generally secretogranins. These are assumed to facilitate storage and release. Superficially, synapses with a thinner postsynaptic specialization, of about the same thickness as that at the presynaptic membrane (hence termed symmetrical ), are often inhibitory; those with a thickened postsynaptic membrane (asymmetrical ) are often excitatory.

Monoaminergic synapses, however, are often asymmetrical, as are those for peptide-containing neurons that do not obey these simple physiological categorizations. Synapses can also be discriminated on the basis of the pairs of neuronal structures that come together at this site of functional transmission. Most typical is the axo-dendritic synapse in which the axon of the presynaptic neuron contacts either the smooth or spiny surface of the dendrite of the post-synaptic neuron. A second common form is the axo-somatic synapse in which the presynaptic axon contacts the surface of the post-synaptic neuron's cell body (or somata). Less frequently observed are axo-axonic relationships in which one axon contacts a second axon-terminal that is in its own axo-dendritic relationship; such triads of axo-axo-dendritic synapses are found most frequently in spinal cord and certain midbrain structures, in which channels of information flow are necessarily highly constrained. Most rarely, junctions between cell bodies (somato-somatic) and dendrites (dendro-dendritic) have also been described.

The nature of the proteins that provide for the thickened appearances of the active zones by electron microscopy are not completely known, but they include the postsynaptic receptors and associated molecules that can transduce the signals from the activate receptors, as well as those molecules that serve to concentrate the receptors in such locations.

(See also: Brain Structures and Drugs ; Neurotransmission ; Reward Pathways and Drugs )

BIBLIOGRAPHY

Bloom, F. E. (1990). Neurohumoral transmission in the central nervous system. In A. G. Gilman et al. (Eds.), Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. Pergamon.

Cooper, J. C., Bloom, F. E., & Roth, R. H. (1991). The biochemical basis of neuropharmacology, 6th ed. New York: Oxford University Press.

Floyd Bloom