ALTERED INTERNEURON-MEDIATED INHIBITION UNDERLIES BROADENED SENSORY TUNING IN S1 DURING ACUTE PAIN

Sensory processing in the primary somatosensory cortex (S1) requires precise coordination between excitatory and inhibitory neurons. We investigated how pyramidal neurons (PYRs), Somatostatin (SST), and Vasoactive Intestinal Peptide (VIP) interneurons in S1 layer 2/3 encode noxious stimuli and adapt during inflammatory pain. Using in vivo two-photon calcium imaging in awake mice, we found that under baseline conditions, PYRs exhibit spatially tuned responses to noxious stimulation, whereas SST neurons provide broad, non-selective inhibition.
Following inflammation induced by complete Freund’s adjuvant (CFA), PYR receptive fields expanded significantly, and spatial tuning degraded. While SST activity remained broad, VIP neurons exhibited altered tuning that mirrored the disruption seen in PYRs. Chemogenetic inhibition of VIP neurons in naive mice unexpectedly sharpened PYR tuning but severely compromised spatial fidelity, causing responsive ensembles to scatter away from the correct somatotopic location. This suggests that VIP neurons are critical not only for regulating receptive field size but for maintaining the coherent spatial organization of cortical maps.
In the pain state, PYR activity increased in response to stimulation of skin regions corresponding to secondary hyperalgesia. These findings indicate that inflammation-induced dysfunction in VIP circuits destabilizes S1 tactile maps, causing inputs from surrounding skin to be misrepresented. This circuit-level reorganization provides a potential mechanism for the spatial spreading of pain sensitivity (secondary hyperalgesia) and allodynia, highlighting the pivotal role of VIP interneurons in pathological sensory processing.