Cortical TRPV1 modulates sensory processing through TRPA1-dependent mechanisms

Abstract Transient receptor potential vanilloid 1 (TRPV1) is classically recognised as a peripheral ion channel involved in nociception, but its physiological role in cortical sensory processing remains poorly understood. Here, we investigated whether cortical TRPV1 modulates tactile perception and sensory representations in the vibrissal primary somatosensory cortex (vS1) of mice. TRPV1 activation enhanced perceptual sensitivity, particularly for near-threshold tactile stimuli. In vS1, this was accompanied by stimulus-evoked responses that enhanced stimulus selectivity and discriminability. At the cellular level, activating TRPV1 increased excitability of pyramidal neurons in a TRPA1-dependent manner. Within vS1, TRPV1 activation reduced positive noise correlations and improved stimulus decoding through TRPA1-dependent changes in population activity. Together, these findings identify a TRPV1-TRPA1 signalling mechanism that regulates cortical gain, sharpens sensory representations and enhances perceptual sensitivity. Our results extend the established role of TRPV1 beyond peripheral sensory transduction to central sensory computation.