Expression of GABA and GABAA receptors by neurons of the subplate zone in developing primate occipital cortex: evidence for transient local circuits.

Several lines of evidence suggest that the transient subplate zone of the embryonic mammalian telencephalon could influence cortical development through synaptic or trophic interactions with growing cortical afferents and migrating neurons. Since such interactions may involve neurotransmitters and their receptor molecules, we have examined the expression of GABA and subunits of the GABAA/benzodiazepine receptor complex in the occipital lobe of embryonic rhesus monkeys by immunochemistry and in situ hybridization. We found that during the second half of gestation, when the subplate zone reaches peak maturity in this species, many neurons can be immunolabeled with both GABA antisera and monoclonal antibodies against GABAA receptor subunits. The most robust labeling occurs at approximately embryonic day (E)125 (birth is at E165). Electron microscopic observations of receptor subunit-immunolabeled material confirmed that subunits of the GABAA receptor are localized in the subplate neurons and their dendritic processes. In many instances the reaction product is associated with the plasma membranes of labeled processes, some of which form symmetrical synapses with small unlabeled axon terminals. The results of in situ hybridization are in accord with the results of receptor subunit immunochemistry. From E80 to E141, hybridization signal for GABAA receptor subunit mRNA occurs in the subplate zone and increases steadily to peak levels between E125 and E141. The present results reveal that all the elements necessary for the formation of functional GABAergic synaptic circuitry are present in the subplate zone. Further, the ages showing the most pronounced receptor and transmitter expression in this primate coincide with the ingrowth of major cortical afferent systems. Taken together, these findings suggest that GABAergic local neuronal circuits in the subplate may be involved in the development of long tract connections stationed in this zone prior to their transfer to the overlying cortical plate.