Neurophysiology of inhibitory and excitatory amino acid receptors

Progress in understanding the workings of the vertebrate brain has been unprecedented over the last half century. Much of this advancement has paralleled our understanding of the myriad roles fulfilled by inhibitory and excitatory amino acid neurotransmitter receptors. It seems surprisingly now that interest in amino acid neurotransmitter receptors started with little fanfare. Instead, there was a gradual appreciation amongst the scientific community that the small, endogenous amino acids, l-glutamic acid (l-Glu), γ-aminobutyric acid (GABA) and glycine (Gly), act on pharmacologically distinct neurotransmitter receptor families (Krnjevic, 2010). With the introduction of better pharmacological tools, the pace of progress quickened as it became possible to systematically map out their distribution in the CNS (Fagg & Foster, 1983). By the end of the 1980s, cloning studies gave our first peek at the molecular diversity of the many subunits that make up each receptor superfamily (Grenningloh et al. 1987; Schofield et al. 1987; Hollmann et al. 1989). With their identity known, an entirely new era ensued as more and more molecular techniques and disciplines were brought to bear on deconstructing inhibitory and excitatory neurotransmission. Now, at the close of these last two decades of rapid progress, we are challenged with putting it all back together if the nature of behaviour and disease is to be finally understood.