Several amino acids have been implicated as neurotransmitters in the CNS, including γ-aminobutyric acid (GABA), glutamic acid, glycine, and aspartic acid. Of these, we know the most about the role of GABA. It was the first amino acid to be established as a neurotransmitter in vertebrate and invertebrate nervous systems. GABA is synthesized in nervous tissue by the alpha decarboxylation of glutamic acid in the presence of glutamic acid decarboxylase (Fig. 17-8).

GABA has usually been described as an inhibitory neurotransmitter and may function primarily in this role in the CNS. It is unusual among amino acids in that it is produced almost exclusively in the brain and spinal cord. Its importance is evidenced by its wide distribution, which has been estimated to include up to one-third of all CNS synapses. The possibility exists that all of the inhibitory cells of the cerebellar cortex are "GABAergic." This includes the Purkinje, stellate, basket, and granular cells. G ABA is also suspected to operate as an inhibitory neurotransmitter in the cerebral cortex, lateral vestibular nucleus, and spinal cord. Chemical analysis has also established the presence of G ABA in the colliculi, diencephalon, and to a lesser extent, the pons, medulla, and much of the cerebral cortex. GABA produces inhibition by hyperpolarizing membranes through increased CI- and K + ion conductance. Glycine, another amino acid transmitter, is also suspected to be inhibitory through the same mechanism. Interestingly enough, glutamic acid, the GABA precursor which chemically differs from it by having two rather than one carboxyl groups, is considered to be an excitatory rather than an inhibitory transmitter. Aspartic acid also appears to be an excitatory transmitter in the spinal cord gray matter. It appears to be associated with interneurons and may oppose the inhibiting action of glycine or GABA-releasing inhibitory interneurons. The formation of these amino acid transmitters from TCA cycle intermediates is illustrated in Fig.