Localization of two major GABA(A) receptor subunits in the dentate gyrus of the rat and cell type-specific up-regulation following entorhinal cortex lesion

GABA(A) receptor subunits show a specific regional distribution in the CNS during development and in the adult animal. In the hippocampal formation, i ndividual subsets of GABAergic interneurons are highly immunoreactive for t he alpha1-subunit, whereas granule and pyramidal cells show a strong expres sion of the alpha2-subunit. Using confocal microscopy and digital image ana lysis, we demonstrate that in the dentate gyrus the alpha1-subunit immunola beling appears in differently sized clusters. The large clusters, which are confined to dendrites of interneurons, show no alpha2 labeling, whereas th e smaller ones coincide with alpha2-subunit-positive clusters. In the molec ular layer, the clusters of both ol-subunits co-localize with the anchoring protein gephyrin. In the granule cell layer and hilus, we found alpha1- an d alpha2-subunit-positive clusters which were devoid of gephyrin labeling. Lesions of the medial entorhinal cortex led to the deafferentation of dendr ites in the middle molecular layer of the dentate gyrus. This resulted in a significantly increased concentration of alpha2-subunit-positive clusters. We also observed an increase of alpha1-subunit immunolabeling in the deaff erented area. We found no change in the co-localization between alpha1 and alpha2, and no significant change in the number of large alpha1-positive cl usters along individual dendritic segments of interneurons. In a previous s tudy, we demonstrated that calbindin-immunoreactive dendrites of granule ce lls revealed a significant increase in gephyrin immunoreactivity following lesion, whereas pan albumin-positive dendrites showed no such alterations. The predominant localization of small gephyrin clusters in dendrites of gra nule cells, which was also described in this study, leads to the conclusion that the increase of the alpha2-subunit-positive clusters, demonstrated in the present study, indicates that, following entorhinal cortex lesion, new GABAergic synapses may be formed and that they contact predominantly granu le cell dendrites, (C) 2001 IBRO. Published by Elsevier Science Ltd. All ri ghts reserved.