Evolution of neurotransmitter gamma-aminobutyric acid, glutamate and their receptors

Gamma-aminobutyric acid (GABA) and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite diversified across different animal phyla. However, the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive, and antagonistic interactions between GABA and glutamate signal transduction systems, in particular, have begun to attract significant attention. In this review, we summarize the extant results on the origin and evolution of GABA and glutamate, as well as their receptors, and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors. We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter (EAAT), a transport protein, which plays an important role in the GABA-glutamate “yin and yang” balanced regulation. Finally, based on current advances, we propose several potential directions of future research.