Functional specialization of hippocampal somatostatin-expressing interneurons.

Abstract

Hippocampal somatostatin-expressing (<i>Sst</i>) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive <i>Sst</i>-IN subpopulations census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of <i>Sst</i>-INs based on transcriptomic features. Four mouse models based on single or combinatorial Cre- and Flp- expression differentiated functionally distinct subpopulations of CA1 hippocampal <i>Sst-</i>INs that largely tiled the morpho-functional parameter space of the <i>Sst</i>-INs superfamily. Notably, the <i>Sst;;Tac1</i> intersection revealed a population of bistratified INs that preferentially synapsed onto fast-spiking interneurons (FS-INs) and were sufficient to interrupt their firing. In contrast, the <i>Ndnf;;Nkx2-1</i> intersection identified a population of oriens lacunosum-moleculare INs that predominantly targeted CA1 pyramidal neurons, avoiding FS-INs. Overall, our results provide a framework to translate neuronal transcriptomic identity into discrete functional subtypes that capture the diverse specializations of hippocampal <i>Sst</i>-INs.