Novel long-range inhibitory nNOS-expressing hippocampal cells

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Abstract

The hippocampus, a brain region important for spatial navigation and episodic memory, benefits from a rich diversity of neuronal cell-types. Through the use of an intersectional genetic viral vector approach in mice, we report novel hippocampal neurons which we refer to as LINCs, as they are long-range inhibitory neuronal nitric oxide synthase (nNOS)-expressing cells. LINCs project to several extrahippocampal regions including the tenia tecta, diagonal band, and retromammillary nucleus, but also broadly target local CA1 cells. LINCs are thus both interneurons and projection neurons. LINCs display regular spiking non-pyramidal firing patterns, are primarily located in the stratum oriens or pyramidale, have sparsely spiny dendrites, and do not typically express somatostatin, VIP, or the muscarinic acetylcholine receptor M2. We further demonstrate that LINCs can strongly influence hippocampal function and oscillations, including interregional coherence. Identification and characterization of these novel cells advances our basic understanding of both hippocampal circuitry and neuronal diversity.

Data availability

All data used for analysis in this publication are included in the manuscript and supporting files. Source data has been included for Table 1. Custom MatLab code is available through GitHub, Inc. at https://github.com/KM-Lab/SpectrumAndCoherence.

Article and author information

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Zoé Christenson Wick

Graduate Program in Neuroscience, University of Minnesota, Minneapolis, United States

For correspondence
chri3433@umn.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2752-0140
Madison R Tetzlaff

Neuroscience Department, University of Minnesota, Minneapolis, United States

Competing interests
The authors declare that no competing interests exist.
Esther Krook-Magnuson

Neuroscience Department, University of Minnesota, Minneapolis, United States

For correspondence
ekrookma@umn.edu

Competing interests
The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01-NS104071)

Esther Krook-Magnuson

National Institutes of Health (F31-NS105457)

Zoé Christenson Wick

University of Minnesota (MnDRIVE (Minnesota's Discovery Research and Innovation Economy) initiative)

Zoé Christenson Wick
Esther Krook-Magnuson

University of Minnesota (McKnight Land-Grant Professorship)

Esther Krook-Magnuson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental protocols were performed in strict accordance with and approved by the University of Minnesota's Institutional Animal Care and Use Committee (protocol # 1801-35497A).

Copyright

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.