A latent pool of neurons silenced by sensory-evoked inhibition can be recruited to enhance perception

SUMMARY Which patterns of neural activity in sensory cortex are relevant for perceptual decision-making? To address this question, we used simultaneous two-photon calcium imaging and targeted two-photon optogenetics to probe barrel cortex activity during a perceptual discrimination task. Head-fixed mice discriminated bilateral whisker deflections and reported decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3 while most neurons did not show task-related activity. Activating small groups of pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by the optogenetic activation of a small number of non-coding neurons, which did not show sensory or motor-related activity during task performance. Patterned photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results provide a novel perspective on the circuit basis for the sparse coding model of somatosensory processing in which a pool of non-coding neurons, selectively suppressed by strong network inhibition during whisker stimulation, can be recruited to enhance perception. Highlights All-optical interrogation of barrel cortex during bilateral whisker discrimination Sparse coding of contralateral and ipsilateral whisker information Selective sensory-evoked inhibition helps ensure sparse coding Optogenetic recruitment of stimulus non-coding neurons can aid perception