Abstracts

The [delta] subunit of the GABA[sub]A[/sub] receptor is distributed diffusely throughout the molecular layer of the dentate gyrus and is also present in some GABAergic interneurons within the hippocampal formation. Many of these interneurons are only lightly labeled in normal adult mice. However, in a pilocarpine mouse model of recurrent seizures, the [delta] subunit labeling of some interneurons increases substantially. These changes are of particular interest because they could be associated with increased tonic inhibition of some GABAergic interneurons and, thus, less effective inhibition of the principal cells. To further characterize these interneurons in normal animals, [delta] subunit expression was studied during the first few weeks of postnatal life. The goal was to determine if all subpopulations of GABAergic interneurons express the [delta] subunit of the GABA[sub]A[/sub] receptor during normal development. C57BL/6 mice were prepared for histological study at regular intervals from 5 to 35 postnatal days. Sections were processed for immunohistochemical localization of the [delta] subunit of the GABA[sub]A[/sub] receptor with a subunit-specific antiserum, and labeled neurons were mapped within the hippocampal formation at each age. During the second and third postnatal weeks, [delta] subunit labeling of interneurons was higher than in adult mice. Within the dentate gyrus, strongly labeled interneurons were present along the inner border of the granule cell layer and within the molecular layer. However, few [delta] subunit-labeled interneurons were evident in the hilus. Within the hippocampal formation, many [delta] subunit-labeled interneurons were present in the pyramidal cell layer of CA1-CA2. Numerous labeled interneurons with fine dendritic processes were also observed in stratum lacunosum-moleculare. In contrast, relatively few [delta] subunit-labeled interneurons were found in these regions of CA3. By four to five postnatal weeks, [delta] subunit labeling had decreased in many interneurons. As a result, only small numbers of labeled interneurons were evident in strata pyramidale and lacunosum moleculare of CA1, and labeled interneurons were sparse in the molecular layer of the dentate gyrus of mature mice. The patterns of labeling throughout the postnatal period suggest that somatostatin neurons in the hilus do not contain the [delta] subunit. : These findings demonstrate that many, but not all, groups of GABA neurons transiently express the [delta] subunit of the GABA[sub]A[/sub] receptor during early postnatal development. The normal lack of [delta] subunit labeling in subgroups of GABAergic interneurons, such as those in the hilus and many in CA3, suggests that [delta] subunit-mediated tonic inhibition may be limited in these interneurons. (Supported by NIH Grant NS35985 and VA Medical Research Funds.)