Novel long-range inhibitory nNOS-expressing hippocampal cells

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.

Hippocampal hub neurons maintain distinct connectivity throughout their lifetime

“…Combined with the fact that biocytin-filled ebGABAs exhibited little local axonal arborization, these data indicate that ebGABAs could form several classes of projection cells innervating various target regions. EbGABAs also share some similarities with the recently described long-range inhibitory nNOS+ cells (LINCs) 42 , in particular laminar location and various long-range targets. However, overlap between these two classes could be small because LINCs are born later (E11.5) and rarely express SOM.…”

Auditory Long-Range Parvalbumin Cortico-Striatal Neurons

“…Do CS-Parv neurons modulate network oscillation (Buzsáki and Draguhn, 2004 ; Buzsáki and Wang, 2012 )? Do CS-Parv neurons have different embryonic development as already demonstrated for the long-range GABAergic hippocampal neurons (Picardo et al, 2011 ; Christenson Wick et al, 2019 )? Do CS-Parv neurons have different gene expression profiles (for review see Huang and Paul, 2019 )?…”

Parvalbumin interneurons provide spillover to newborn and mature dentate granule cells

“…The slow kinetics, high sensitivity to TPMPA and robust effects of NO711 of PV-evoked GPSCs in newborn GCs are characteristic of GPSCs evoked by ivy/neurogliaform interneurons, slow-spiking GABAergic interneurons that signal via volume transmission that lacks postsynaptic anatomical specializations ( Szabadics et al, 2007 ; Oláh et al, 2009 ; Karayannis et al, 2010 ; Overstreet-Wadiche and McBain, 2015 ). A large fraction of ivy/neurogliaform cells express neuronal nitric oxide synthase (nNOS) ( Tricoire et al, 2010 ; Gonzalez et al, 2018 ; Christenson Wick et al, 2019 ), so to compare slow GPSCs evoked by PVs and ivy/neurogliaform interneurons, we also bred nNOS-CreER:(H134R)-EYFP:Pomc-EGFP mice that were treated with tamoxifen after weaning ( Figure 3C ). In contrast to PVs, nNOS interneurons exhibited extensive processes in the hilus and molecular layer but not the GCL, and light-pulses up 5 ms in duration triggered single rather than multiple spikes ( Figure 3—figure supplement 1A,B ).…”