A SPINORETICULAR PATHWAY MEDIATES DEFENSIVE RESPONSES TO NOXIOUS MECHANICAL STIMULI

Spinal projection neurons (SPNs) play essential role in relaying somatosensory input to the brain, yet how genetically defined SPN subsets route noxious mechanical signals to supraspinal targets to support defensive behaviors remains unclear. Using intersectional genetic labeling combined with anatomical tracing and functional manipulation in mice, we demonstrated that a population of Sncg-expressing SPNs, which project predominantly to the parabrachial nucleus (PBN) and the lateral reticular nucleus (LRN), is critical for processing mechanical sensation. We showed that Sncg⁺ spinoparabrachial (SPB) and spinoreticular (SRT) pathways are differentially engaged in processing innocuous and noxious mechanical sensory information, respectively. We further demonstrate that LRN neurons which receive Sncg⁺ spinal neuron projection are required for driving nocifensive behaviors in response to noxious mechanical stimulation. Finally, we identified local spinal interneurons that directly innervate Sncg⁺ SPNs, providing an entry point for spinal control of this output channel. Together, these findings define Sncg-expressing SPNs as a genetically defined ascending relay that routes mechanical sensory signals and reveal a spinoreticular ascending pathways mediating defensive responses to noxious mechanical stimuli.