A ventrodorsal GABA gradient in the embryonic retina prior to expression of glutamate decarboxylase

GABA is known to function as a neurotransmitter in the mature nervous system, and in immature neurons it has been linked to neurotrophic actions. While most GABA is generated by glutamate decarboxylase (GAD), an alternative synthetic pathway is known to originate from putrescine, which is converted via gamma-aminobutyraldehyde in an aldehyde-dehydrogenase-requiring step to GABA. In a search for the role of two aldehyde dehydrogenases expressed in segregated compartments along the dorsoventral axis of the developing retina, we assayed dorsal and ventral retina fractions of the mouse for GABA by high performance liquid chromatography. We found GABA to be present in the embryonic retina, long before expression of GAD, and ventral GABA levels exceeded dorsal levels by more than three-fold. Postnatally, when GAD became detectable, overall GABA levels increased, and the ventrodorsal concentration difference disappeared. Our observations indicate that prior to the formation of synapses the embryonic retina contains a ventrodorsal GABA gradient generated by an alternate synthetic pathway.