GABA AND GABA-A RECEPTORS ARE MAXIMALLY EXPRESSED IN ASSOCIATION WITHCONE SYNAPTOGENESIS IN NEONATAL RABBIT RETINA

Previous studies have shown the cone photoreceptors form reciprocal sy napses with horizontal cells during the first week after birth in rabb its. These synapses constitute pioneering elements of the developing o uter plexiform layer. We now report that antibodies against the alpha- 1 and against the beta-2/3 subunits of the GABA-A receptor label a hig hly restricted sublamina in the developing outer plexiform layer known to contain nascent cone photoreceptor terminals. Staining is relative ly weak at birth, increases to maximal levels between postnatal days 5 and 7, and is significantly reduced in the adult. These results suppo rt recent calcium imaging studies which have shown that the activation of GABA-A receptors causes an increase in intracellular free calcium in cones, an effect which is observed only at 3-9 days after birth. Th e transient expression of GABA-A receptors in this region coincides wi th the period of peak expression of GABA immunoreactivity in horizonta l cells. A direct functional Link between GABAergic transmission and c one synaptogenesis is suggested by previous reports that GABA-A recept or antagonists cause disruption of cone synaptogenesis. Together these findings support the notion that GABA functions as a developmental ne urotransmitter which is produced by horizontal cells and interacts wit h developing cone axons in order to facilitate synaptic linkage betwee n the:se two cells types.