biostudies-literatureGauld OMEuropean Research CouncilUKRI Medical Research CouncilMedical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Council2386-2403.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616379biostudies-literatureUnknown112(14)To investigate which activity patterns in sensory cortex are relevant for perceptual decision-making, we combined two-photon calcium imaging and targeted two-photon optogenetics to interrogate barrel cortex activity during perceptual discrimination. We trained mice to discriminate bilateral whisker deflections and report decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3, with most neurons remaining silent during the task. Activating pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by optogenetic activation of non-coding neurons, which did not show sensory or motor-related activity during task performance. Photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results suggest that a pool of non-coding neurons, selectively suppressed by network inhibition during sensory processing, can be recruited to enhance perception.NeuronA latent pool of neurons silenced by sensory-evoked inhibition can be recruited to enhance perception.PMC7616379AdG 695709MR/T022922/1PRF 201225224688201225BB/N009835/1224668695709Packer AMDalgleish HWPIuga MClark BARussell LESacadura FGauld OMRoth AHausser MfalseA latent pool of neurons silenced by sensory-evoked inhibition can be recruited to enhance perception.To investigate which activity patterns in sensory cortex are relevant for perceptual decision-making, we combined two-photon calcium imaging and targeted two-photon optogenetics to interrogate barrel cortex activity during perceptual discrimination. We trained mice to discriminate bilateral whisker deflections and report decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3, with most neurons remaining silent during the task. Activating pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by optogenetic activation of non-coding neurons, which did not show sensory or motor-related activity during task performance. Photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results suggest that a pool of non-coding neurons, selectively suppressed by network inhibition during sensory processing, can be recruited to enhance perception.2024-01-01T00:00:00Z2024 Jul2025-04-19T20:38:12.345Z2025-04-19T20:38:12.345ZS-EPMC76163793872915010.1016/j.neuron.2024.04.015