Functional specialization of hippocampal somatostatin- expressing interneurons

• 成果类型: Article
• 署名作者: Chamberland, Simon; Grant, Gariel; Machold, Robert; Nebet, Erica R.; Tian, Guoling; Stich, Joshua; Hanani, Monica; Kullander, Klas; Tsien, Richard W.
• 署名单位: New York University; New York University; Uppsala University; New York University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12118
• DOI: 10.1073/pnas.2306382121
• 发表日期: 2024-04-23
• 关键词: dual intracellular-recordings; transcriptomic cell-types; immunoreactive interneurons; gabaergic interneurons; dendritic inhibition; bistratified cells; pyramidal cells; transgenic mice; neurons; slices

摘要

Hippocampal somatostatinexpressing ( 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 CA! 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 CA! 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. Significance GABAergic interneurons are important regulators of neuronal activity. Recent transcriptome analyses have provided a comprehensive classification of interneurons, but the connections between molecular identities and specific functions are not yet fully understood. Here, we identified and accessed subpopulations of interneurons based on features predicted by transcriptomic analysis. Functional investigation in transgenic animals revealed that hippocampal somatostatinexpressing interneurons ( Sst - INs) can be divided into at least four subfamilies, each with distinct functions. Most importantly, the Sst;;Tac1 intersection targeted a population of bistratified cells that overwhelmingly targeted fast- spiking interneurons. In contrast, the Ndnf;;Nkx2 - 1 intersection revealed a population of oriens lacunosum- moleculare interneurons that selectively targeted CA1 pyramidal cells. Overall, this study reveals that genetically distinct subfamilies of Sst - INs form specialized circuits in the hippocampus.