Selective Allocation of GABAA Receptors Containing the α1 Subunit to Neurochemically Distinct Subpopulations of Rat Hippocampal Interneurons

The identification of a large variety of GABA_A receptor subunits by molecular cloning suggests the existence of multiple receptor subtypes differing in localization and functional properties. In the present study we analysed immunohistochemically the cellular distribution of GABA_A receptors containing the α1 subunit in the rat hippocampus with a subunit-specific antiserum. Prominent staining of numerous interneurons was evident in Ammon's horn and the dentate gyrus, which contrasted with moderate and diffuse immunoreactivity in the dendritic layers of pyramidal and granule cells. Double immunofluorescence staining with antibodies to GABA revealed that a subset of GABAergic neurons in the hippocampus were immunoreactive for the α1 subunit. To determine whether these cells represent distinct subpopulations of interneurons, we analysed the co-localization of the GABA_A receptor α1 subunit with selective markers of hippocampal interneurons (selected calcium-binding proteins and neuropeptides). In both Ammon's horn and the dentate gyrus, all parvalbumin-positive neurons and 50% of calretinin-positive neurons were double-labelled, whereas interneurons containing calbindin-D_28k were devoid of α1 subunit staining. Similarly, most neurons positive for neuropeptide Y and a subset of somatostatin-positive cells were double-labelled, in contrast to cholecystokinin- and vasoactive intestinal peptide-containing cells, which lacked the α1 subunit staining. These results demonstrate cell-specific expression of GABA_A receptors containing the α1 subunit among subsets of hippocampal interneurons, pointing to a pronounced functional specialization of these cells. Furthermore, the prominent expression of GABA_A receptors by interneurons suggests that disinhibition may be of major functional relevance in regulating the balance between excitation and inhibition in hippocampal circuits.