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

Abstract

GABA A receptor subunits show a specific regional distribution in the CNS during development and in the adult animal. In the hippocampal formation, individual subsets of GABAergic interneurons are highly immunoreactive for the α1-subunit, whereas granule and pyramidal cells show a strong expression of the α2-subunit. Using confocal microscopy and digital image analysis, we demonstrate that in the dentate gyrus the α1-subunit immunolabeling appears in differently sized clusters. The large clusters, which are confined to dendrites of interneurons, show no α2 labeling, whereas the smaller ones coincide with α2-subunit-positive clusters. In the molecular layer, the clusters of both α-subunits co-localize with the anchoring protein gephyrin. In the granule cell layer and hilus, we found α1- and α2-subunit-positive clusters which were devoid of gephyrin labeling. Lesions of the medial entorhinal cortex led to the deafferentation of dendrites in the middle molecular layer of the dentate gyrus. This resulted in a significantly increased concentration of α2-subunit-positive clusters. We also observed an increase of α1-subunit immunolabeling in the deafferented area. We found no change in the co-localization between α1 and α2, and no significant change in the number of large α1-positive clusters along individual dendritic segments of interneurons. In a previous study, we demonstrated that calbindin-immunoreactive dendrites of granule cells revealed a significant increase in gephyrin immunoreactivity following lesion, whereas parvalbumin-positive dendrites showed no such alterations. The predominant localization of small gephyrin clusters in dendrites of granule cells, which was also described in this study, leads to the conclusion that the increase of the α2-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 granule cell dendrites.