Principles of Synaptic Transmissiona

Neurons in the central nervous system communicate almost exclusively by the production and release at synapses of a series of molecules that are designated transmitters. Three such molecules make up the major transmitters, GABA, glutamate, and acetylcholine. GABA neurons are the principal inhibitory neurons and, as such, are the major local circuit neurons of the brain. They also are projection neurons in a number of systems. Glutamate neurons are excitatory projection neurons, particularly of the cerebral cortex, thalamus and retina. Acetylcholine neurons are excitatory neurons in ascending brainstem and basal forebrain systems and in cranial and spinal motor neurons and neurons of the sympathetic and parasympathetic systems. The catecholamines, dopamine and norepinephrine, are transmitters in several systems in brain. Dopamine is present in midbrain neurons projecting to the neostriatum, basal forebrain and cerebral cortex. It is also produced by hypothalamic neurons projecting to the median eminence and pituitary. These systems are highly topographically organized in contrast to the norepinephrine systems. The locus coeruleus norepinephrine system projects principally to thalamus, cerebral cortex and cerebellar cortex whereas the lateral tegmental system projects primarily to basal forebrain, hypothalamus, brainstem and spinal cord. The serotonin neurons of the brainstem raphe also project widely over the neuraxis, midbrain raphe neurons primarily to diencephalon and telencephalon and pontine medullary neurons to brainstem and spinal cord. There are smaller neuronal groups that produce glycine or histamine. At the present time, it appears that most, if not all, CNS neurons produce one of these small molecule transmitters. In many instances, these molecules are colocalized with one or more peptides that appear to modify the postsynaptic action of the small molecule transmitter.