A stimulus-state geometry in somatosensory cortex reorganizes during inflammatory pain

Abstract

Adaptive behavior requires external input to be interpreted together with internal state and ongoing behavior. During pain, noxious somatosensory input evokes movement and arousal, and injury reshapes this relationship, yet how cortical activity organizes stimulus content with behavioral state remains unclear. In awake mice, we delivered hindpaw stimuli while tracking movement, arousal and facial expression, and studied primary somatosensory cortex (S1) using widefield and two-photon calcium imaging, single-action-potential activation of nociceptors, and S1 silencing. Here, we show that S1 neurons were broadly recruited by stimulus and state, whereas latent population dimensions carried mechanical stimulus content. Inflammatory injury caused a reorganization of S1 geometry, binding state and protective responses tighter together. Noxious heat drove S1 as strongly, but engaged mostly the state axis. S1 silencing reduced mechanical hypersensitivity, arousal, and facial expressions. S1 thus embeds mechanical input within a stimulus-state geometry, which is reorganized during inflammatory injury to support adaptation of a coordinated protective response.