GABA as a trophic factor during development

The process of synaptogenesis has been studied by many investigators to determine the factors which regulate synapse formation. We have used neonatal rabbit retina to investigate the role of the gamma-aminobutyric acid (GABA) neurotransmitter system during development. By utilizing an in vitro incubation treatment of isolated eyecups we found that treatment with nipecotic acid, a GABA uptake blocker, resulted in a 4-fold increase in the amount of specific 3H-muscimol binding. In addition, incubation of the tissue in the presence of the GABA agonists muscimol, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol (THIP), or GABA itself led to similar increases in specific 3H-muscimol binding. The findings support the conclusion from previous studies that the induction of GABA receptors observed after in vivo treatment of 1-day-old rabbits with nipecotic acid resulted from an increase in the extracellular concentration of GABA. A possible role for GABA in the regulation of GABAergic synapse formation is presented in this report.