Functional specialization of hippocampal somatostatin-expressing interneurons

Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2306382121. doi: 10.1073/pnas.2306382121. Epub 2024 Apr 19.

Abstract

Hippocampal somatostatin-expressing (Sst) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive Sst-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 Sst-INs based on transcriptomic features. Four mouse models based on single or combinatorial Cre- and Flp- expression differentiated functionally distinct subpopulations of CA1 hippocampal Sst-INs that largely tiled the morpho-functional parameter space of the Sst-INs superfamily. Notably, the Sst;;Tac1 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 Ndnf;;Nkx2-1 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 Sst-INs.

Keywords: circuits; disinhibition; hippocampus; inhibition; somatostatin interneurons.

MeSH terms

  • Animals
  • Hippocampus* / metabolism
  • Interneurons* / physiology
  • Mice
  • Neurons / metabolism
  • Pyramidal Cells / metabolism
  • Somatostatin / genetics
  • Somatostatin / metabolism

Substances

  • Somatostatin