The hippocampus, a brain region that is 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. The identification and characterization of these novel cells advances our basic understanding of both hippocampal circuitry and neuronal diversity.
Bibliographical noteFunding Information:
The authors would like to thank Gord Fishell and his lab, including Robert Machold, Goichi Miyoshi, and Rowena Turnbull for providing the Dlx5/6-Flpe and RCE:dual reporter mouse lines, and Karl Deisseroth and Charu Ramakrishnan for the intersectional virus. We thank the University of Minnesota University Imaging Centers for tissue clearing and imaging and technical support, with special assistance from Director Mark Sanders. Additional thanks to the entire Krook-Magnuson lab, in particular to Casey Xamonthiene for expertise in tissue processing, Chris Krook-Magnuson for MATLAB programming assistance, Zachary Zeidler for assistance with behavior experimental design and confocal imaging, Zachary Montes, and Isaac Hoff for assistance with behavioral experiments, Caara H. Leintz for early assistance with stereotactic surgeries, and Bethany Stieve for helpful discussions and confocal imaging assistance. This work was supported by the National Institutes of Health grants R01-NS104071 (to EKM) and F31-NS105457 (to ZCW), the University of Minnesota’s MnDRIVE (Minnesota’s Discovery, Research, and Innovation Economy) initiative (to EKM & ZCW), and a McKnight Land-Grant Professorship (to EKM).
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PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural