Abstract
The primary somatosensory cortex (S1) is the hub for body sensation of both innocuous and noxious signals, yet its role in somatosensation versus pain is debated. Despite known contributions of S1 to sensory gain modulation, its causal involvement in subjective sensory experiences remains elusive. Unspecific bulk manipulations of S1 activity have not disambiguated the precise role of the S1 in nociception and pain. Here, using cell-type-specific manipulations in mouse S1 we reveal the involvement of two major cortical output neuron types in layers 5 (L5) and 6 (L6) in the perception of innocuous and noxious somatosensory signals. We find that L6 neurons can drive aversive hypersensitivity and spontaneous nocifensive behavior. L6 downstream effects revealed enhanced thalamic somatosensory responses, and in parallel, strong suppression of L5 neurons, pointing towards an antinociceptive function of L5 output. Indeed, targeted L5 activation reduced sensory sensitivity and normalized inflammatory allodynia, thus revealing a layer-specific and bidirectional role for S1 in modulating subjective sensory experiences.
Competing Interest Statement
The authors have declared no competing interest.
