The article by Eugene Roberts is an accurate and clear statement of the historical and physiological aspects of GABA as a neurotransmitter. It adds interesting insights into the natural selection and properties of this small molecule , and shows its important role in the larger picture of the brain circuitry and in the balancing actions that are critical for the incredibly complex signalling therein .In my opinion this article is fine as it stands. Eric A. Barnard
This article is suitable for publication and contains valuable information. I suggest some non-mandatory minor changes if the author agrees. It is my opinion that the basic neurophysiology and neurochemistry are correct while containing novel views. Some of the points probably ought to be referenced. In the neurochemistry section describing the the GABA shunt, it might be nice to clarify the sentence about 'substrate level phosphorylation of GDP' by noting that this pathway uses an enzyme different from that in the Krebs cycle (alpha-keto glutarate dehydrogenase) that normally would generate one equivalent of GTP which does not occur with the GABA shunt. I think the section on the 'inhibited nervous system'is a major strength of the article. The section on the quintessential neurotransmitter is marginally important, but sufficiently novel to be included. The part about GABA and diseases of the CNS could be easily expanded to give some more recent evidence, e.g., the discovery of mutations in GABA-A receptors in some types of human epilepsy, and the verification by genetically engineered mice that GABA receptor dysfunction can cause epilepsy. One review reference might suffice. Overall this ia a nice contribution and should be accepted.