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Functional specialization of hippocampal somatostatin-expressing interneurons.

Simon ChamberlandGariel GrantRobert MacholdErica R NebetGuoling TianJoshua StichMonica HananiKlas KullanderRichard W Tsien
Published in: Proceedings of the National Academy of Sciences of the United States of America (2024)
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.
Keyphrases
  • single cell
  • rna seq
  • cerebral ischemia
  • poor prognosis
  • gene expression
  • magnetic resonance
  • mouse model
  • high throughput
  • dna methylation
  • magnetic resonance imaging
  • transcription factor
  • subarachnoid hemorrhage