Novel long-range inhibitory nNOS-expressing hippocampal cells.

Zoé Christenson Wick,Esther Krook-Magnuson,Madison R Tetzlaff

doi:10.7554/elife.46816

Zoé Christenson Wick, Esther Krook-Magnuson + Show 1 more

Open Access

https://doi.org/10.7554/elife.46816

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Journal: eLife	Publication Date: Oct 14, 2019
Citations: 28	License type: CC BY 4.0

Affiliation: University of Minnesota

Abstract

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.

Highlights

The hippocampus is one of the most extensively studied brain regions (Andersen et al, 2007), and in CA1 alone, more than 20 types of inhibitory neurons have been previously described (Freund and Buzsaki, 1996; Klausberger and Somogyi, 2008)
This approach limits the expression of enhanced yellow fluorescent protein (eYFP)-tagged ChR2 to neuronal nitric oxide synthase (nNOS)-expressing interneurons (Figure 1c), nNOS-expression was difficult to detect in some labeled neurons and not all nNOS-immunopositive cells expressed eYFP (Figure 1—figure supplement 1)
LINCs could be labeled with a viral injection targeting either the dorsal or ventral CA1 stratum oriens, with virally labeled cells found along the anterior-posterior extent of the hippocampus at a considerable distance from the site of injection (Figure 2a; Figure 2—figure supplement 1), suggestive of widespread processes

Summary

Introduction

The hippocampus is one of the most extensively studied brain regions (Andersen et al, 2007), and in CA1 alone, more than 20 types of inhibitory neurons have been previously described (Freund and Buzsaki, 1996; Klausberger and Somogyi, 2008). Despite extensive prior investigation of the neuronal populations in CA1 (reviewed by Freund and Buzsaki, 1996, Klausberger and Somogyi, 2008 and Pelkey et al, 2017), recent work highlights that some cell types still lack proper characterization (Harris et al, 2018). LINCs express nNOS and possess long-range axons, they do not appear to be hippocampal versions of cortical NOS-type I cells, nor do they closely match any other previously characterized hippocampal cell population, as detailed in depth below. Despite being relatively few in number, the properties of LINCs suggest that they can have a surprisingly robust impact on hippocampal network function, oscillatory dynamics, and inter-regional coherence

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Conclusion