Abstract
The superficial dorsal horn (SDH, LI-II) of the spinal cord receives and processes multimodal sensory information from skin, muscle, joints, and viscera then relay it to the brain. Neurons within the SDH fall into two broad categories, projection neurons and interneurons. The later can be further subdivided into excitatory and inhibitory types. Traditionally, interneurons within the SDH have been divided into overlapping groups according to their neurochemical, morphological and electrophysiological properties. Recent clustering analyses, based on molecular transcript profiles of cells and nuclei, have predicted many more functional groups of interneurons than expected using traditional approaches. In this study, we used electrophysiological and morphological data obtained from genetically-identified excitatory (vGLUT2) and inhibitory (vGAT) interneurons in transgenic mice to cluster cells into groups sharing common characteristics and subsequently determined how many clusters can be assigned by combinations of these properties. Consistent with previous reports, we show differences exist between excitatory and inhibitory interneurons in terms of their excitability, nature of the ongoing excitatory drive, action potential (AP) properties, sub-threshold current kinetics, and morphology. The resulting clusters based on statistical and unbiased assortment of these data fell well short of the numbers of molecularly predicted clusters. There was no clear characteristic that in isolation defined a population, rather multiple variables were needed to predict cluster membership. Importantly though, our analysis highlighted the appropriateness of using transgenic lines as tools to functionally subdivide both excitatory and inhibitory interneuron populations.
Highlights
The superficial dorsal horn (SDH) of the spinal cord receives and processes primary afferent input conveying noxious, thermal, tactile, and pruritic sensory signals from the body destined for the brain
The following results include data from 198 dorsal horn neurons recorded in the SDH of spinal cord slices prepared from VGAT:TdTomato and VGLUT2-positive neurons with a green fluorescent protein (VGLUT2):TdTomato mice
Four-cell groups are differentiated and reported on: (1) targeted inhibitory interneurons (VGAT+, n = 76); (2) putative excitatory interneurons (VGAT−, n = 57); (3) targeted excitatory interneurons (VGLUT2+, n = 40); and (4) putative inhibitory interneurons (VGLUT2−, n = 25). It follows that VGAT+ and VGLUT2− samples should come from the same overall population, and likewise, the VGLUT2+ and VGAT− samples should overlap substantially
Summary
The superficial dorsal horn (SDH) of the spinal cord receives and processes primary afferent input conveying noxious, thermal, tactile, and pruritic sensory signals from the body destined for the brain. Recent models of spinal sensory processing have provided a framework for understanding how interneurons contribute to spinal processing mechanisms They have highlighted the important interplay between inhibitory gating mechanisms (Bourane et al, 2015; Foster et al, 2015; Petitjean et al, 2015; François et al, 2017; Sun et al, 2017; Boyle et al, 2019) and polysynaptic excitatory pathways (Torsney and MacDermott, 2006; Takazawa and MacDermott, 2010; Peirs et al, 2015; Takazawa et al, 2017) for normal sensory experience. Similar observations have been reported using tetanus toxin-based silencing of the PV interneurons with detailed optogenetic circuit mapping confirming these cells are a source of presynaptic inhibition on myelinated afferents, as well as mediating postsynaptic inhibition to excitatory interneurons that relay touch-related signals into lamina I (Boyle et al, 2019)
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