Focal infrared stimulation modulates somatosensory cortical activity in mice: evidence for TRPV1 ion channel involvement

Infrared neural stimulation (INS) is a promising approach for minimally invasive modulation of neuronal activity, yet its cellular and molecular mechanisms in the intact brain remain incompletely understood. Here, we investigated focal INS in the somatosensory cortex of anesthetized mice using high-density Neuropixels recordings combined with histological analysis. Continuous-wave and pulsed (500 Hz) infrared illumination elicited robust modulation of cortical activity, with approximately half of recorded neurons exhibiting either increased or suppressed firing. The modulatory effects of stimulation were comparable across cortical layers and neuron types. While both stimulation modes were effective, continuous-wave stimulation typically produced stronger changes in firing rates and network dynamics than pulsed illumination. To explore molecular contributions, we compared responses in wild-type and TRPV1 knockout mice. Neuronal responses to INS were significantly reduced in knockout animals, indicating a key role for TRPV1 channels. We also observed layer- and neuron-type-specific differences in firing rate modulation between wild-type and knockout animals. Histological analysis confirmed that TRPV1-expressing neurons are distributed throughout cortical layers, supporting their involvement in the observed responses. These findings provide direct evidence that TRPV1 contributes to INS-evoked cortical activity and advance our understanding of the mechanisms underlying infrared neuromodulation. This work lays a foundation for the future use of infrared light as a precise and minimally invasive tool for cortical circuit manipulation.