ePoster

Combined electrophysiologic and transcriptomic characterization reveals different functional populations of GABAergic spinal neurons in neuropathic pain mouse model

Charline Kambrun, Florian Specque, Vanessa Rouglan, Alexis Groppi, Macha Nikolski, Alexandre Favereaux, Yves Le Feuvre
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Charline Kambrun, Florian Specque, Vanessa Rouglan, Alexis Groppi, Macha Nikolski, Alexandre Favereaux, Yves Le Feuvre

Abstract

Pain elaboration results from the integration within dorsal spinal cord networks of sensory and nociceptive information conveyed by primary afferents. While many evidence suggest that a major disinhibition of dorsal horn networks may promote enhanced pain transmission in chronic pain pathologies, little is known about inhibitory neurons properties themselves and whether specific inhibitory subpopulations are preferentially altered in chronic pain conditions.We used the Spared Nerve Injury (SNI) neuropathic pain model on Gad67-GFP transgenic mice, which specifically labels dorsal horn inhibitory neurons. Using the patch-seq technique, we recovered both the electrophysiological and transcriptomic properties of individual neurons in acute spinal slices of SNI or SHAM animals.We show that SNI GABAergic neurons within dorsal spinal cord display increased spiking threshold as well as a decreased average EPSC amplitude, compared to SHAM neurons. Strikingly, these alterations did not depend on the observed firing pattern of the recorded neurons. Using the patch-seq method, we collected high quality transcriptomes, exhibiting strong inhibitory neurons features. Strikingly, unsupervised clustering of these neurons revealed the existence of 5 major neuronal subpopulations with specific transcriptomic and electrophysiologic features in SHAM animals. Finally, we show that inhibitory neurons subpopulations are unequally altered in SNI animals: while some subpopulations are mostly unaffected by SNI surgery, some others display strong alterations in spike shape (amplitude and AHP) as well as important decrease of EPSC amplitude.Altogether, our results suggest that different subpopulations of inhibitory neurons may play different roles in the transmission of painful information in neuropathic pain conditions.

Unique ID: fens-24/combined-electrophysiologic-transcriptomic-2718de57