Id2 GABAergic interneurons comprise a neglected fourth major group of cortical inhibitory cells
- New York University, United States
- Hospital del Mar Medical Research Institute (IMIM), Spain
- University of Colorado Boulder, United States
Abstract
Cortical GABAergic interneurons (INs) represent a diverse population of mainly locally projecting cells that provide specialized forms of inhibition to pyramidal neurons and other INs. Most recent work on INs has focused on subtypes distinguished by expression of Parvalbumin (PV), Somatostatin (SST), or Vasoactive Intestinal Peptide (VIP). However, a fourth group that includes neurogliaform cells (NGFCs) has been less well characterized due to a lack of genetic tools. Here, we show that these INs can be accessed experimentally using intersectional genetics with the gene Id2. We find that outside of layer 1 (L1), the majority of Id2 INs are NGFCs that express high levels of neuropeptide Y (NPY) and exhibit a late-spiking firing pattern, with extensive local connectivity. While much sparser, non-NGFC Id2 INs had more variable properties, with most cells corresponding to a diverse group of INs that strongly expresses the neuropeptide CCK. In vivo, using silicon probe recordings, we observed several distinguishing aspects of NGFC activity, including a strong rebound in activity immediately following the cortical down state during NREM sleep. Our study provides insights into IN diversity and NGFC distribution and properties, and outlines an intersectional genetics approach for further study of this underappreciated group of INs.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figures 1, 2, 4, Table 1, Figure 1 - figure supplement 1 and Figure 1 - figure supplement 2.
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Whole Cortex and Hippocampus - 10x genomics (2020) with 10x-Smart-Seq Taxonomyhttps://portal.brain-map.org/atlases-and-data/rnaseq/mouse-whole-cortex-and-hippocampus-10x.
Article and author information
Author details
Funding
National Institutes of Health (P01NS074972)
- Bernardo Rudy
National Institutes of Health (R01NS110079)
- Bernardo Rudy
National Institutes of Health (U19NS107616)
- György Buzsáki
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Ethics
Animal experimentation: All experimental animals were handled with care to minimize suffering in accordance with institutional animal care and use committee (IACUC) protocols approved by the Division of Comparative Medicine at the NYU Langone Medical Center for Dr. Bernardo Rudy's lab (#IA15-01465 and #IA15-01473).
Version history
- Preprint posted: December 1, 2022 (view preprint)
- Received: December 30, 2022
- Accepted: August 21, 2023
- Accepted Manuscript published: September 4, 2023 (version 1)
- Version of Record published: October 17, 2023 (version 2)
Copyright
© 2023, Machold et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Id2 GABAergic interneurons comprise a neglected fourth major group of cortical inhibitory cells
eLife 12:e85893.
https://doi.org/10.7554/eLife.85893
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