Localization of Putative Amino Acid Transmitters in the PAG and their Relationship to the PAG-Raphe Magnus Pathway

Abstract

The vast majority of synapses in the central nervous system (CNS) appear to use excitatory amino acids as their neurotransmitters (Cotman et al., 1987; Monaghan et al., 1989; Watkins et al., 1990). Although Curtis et al. (1959; 1960) first provided conclusive evidence over 3 decades ago that glutamate and aspartate exert a powerful excitatory action on neurons, it was only during the past 15 years that glutamate and aspartate have been seriously considered as excitatory neurotransmitters in the CNS. Several other amino acids and dipeptides have been suggested as putative excitatory amino acid transmitter candidates in the CNS, however, the majority of evidence to date favors glutamate and aspartate as the most likely candidates for neurotransmitters in the brain. Thus glutamate and aspartate have largely been shown to fulfill the criteria for a neurotransmitter, e.g., Ca²⁺-dependent release upon stimulation, high affinity uptake into nerve terminals, presence of the amino acids and synthetic enzymes in nerve terminals, blockade of synaptic transmission by excitatory amino acid antagonists, and identity of action (Cotman et al., 1987; Fonnum, 1984; Nicholls, 1989; Watkins and Evans, 1981).