Parallel Interrogation of Supraspinal Projections, Excitatory, and Inhibitory Neurons in the Naïve Mouse Dorsal Horn

• Published in: The journal of pain Vol. 25; no. 4; p. 18
• Main Authors: Warwick, Charles, Sheahan, Tayler, Cui, Abby, Stratton, Harrison, Koerber, Rick, Ross, Sarah
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2024
• ISSN: 1526-5900; 1528-8447
• DOI: 10.1016/j.jpain.2024.01.090

Every primary afferent contributes information to the spinal dorsal horn (SDH). These Inputs are processed and integrated before being transmitted supraspinally by a small subset of projection neurons and represent an abstracted form of the primary afferent input. The spinal cord is thus, the first significant site of sensory integration and processing and yet, we do not understand how the SDH processes sensory information well enough to target it for the treatment of chronic pain. Here, using an ex vivo skin-nerve preparation and Ca2+ imaging at the dorsal root ganglia (DRG) and the SDH we interrogated the logic and identity of spinal circuits in naïve mice with the eventual goal to understand what changes after the induction of chronic pain. GCaMP6s is expressed pan-neuronally; nuclear mCherry is expressed in the inhibitory neurons and identifies the excitatory neurons by exclusion; superficial projection neurons are labeled via DiI injection at parabrachial nucleus; and sub-populations of each group are pharmacologically identified via receptor expression. The combination of neurochemical identification, anatomical tracing, pharmacological identification, and well controlled cutaneous stimuli provides an unprecedented amount of detail within a single intact sensory system. Preliminary results suggest that inhibitory interneurons are more sensitive to cutaneous stimuli, and sub-populations of both excitatory and inhibitory neurons respond differentially to specific stimuli types and intensities. By and large, projection neurons seem to reflect the summed activity of the superficial excitatory neurons, although subpopulations of these projection neurons do appear to be preferentially responsive to certain kinds of sensory input.