Characterization of spinal dorsal horn neurons expressing the serotonin receptor 5-HT3A

Raw data related to: Characterization of spinal dorsal horn neurons expressing the serotonin receptor 5-HT3A Abstract The function of the ionotropic serotonin receptor 5-HT3A, encoded by Htr3a, in the spinal cord remains controversial, with both pro- and anti-nociceptive effects reported. This controversy may, in part, reflect the incomplete characterization of the cellular populations expressing 5-HT3A in the spinal dorsal horn. Using a newly generated Htr3a FlpO knock-in mouse line, we show that spinal 5-HT3A receptor expression originates from two principal sources: peptidergic (CGRP+) primary afferent nociceptors and a heterogeneous population of inhibitory interneurons in the deep dorsal horn. The inhibitory interneuron population includes subsets defined by parvalbumin (Pvalb), galanin (Gal), and Gbx1 expression, markers of inhibitory neuron subpopulations previously implicated in antinociceptive or anti-allodynic functions. Whole-cell recordings showed that most of these neurons were silent and exhibit a tonic firing pattern upon depolarizing current injection. Local serotonin application did not directly evoke membrane currents in Htr3a neurons but did trigger serotonergic EPSCs, confirming functional 5-HT3A receptor expression. Finally, an intersectional genetic strategy to selectively target inhibitory spinal Htr3a-positive interneurons, revealed that Htr3a-positive primary afferents and inhibitory interneurons occupy largely non-overlapping domains in the dorsal horn and trigeminal nucleus. Together these results provide a cellular framework for understanding the diverse effects of 5-HT3A signaling in nociception.