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The primary somatosensory cortex (S1) plays a critical role in processing multiple somatosensations, but the mechanism underlying the representation of different submodalities of somatosensation in S1 remains unclear. Using in vivo two-photon calcium imaging that simultaneously monitors hundreds of layer 2/3 pyramidal S1 neurons of awake male mice, we examined neuronal responses triggered by mechanical, thermal, or pruritic stimuli. We found that mechanical, thermal, and pruritic stimuli activated largely overlapping neuronal populations in the same somatotopic S1 subregion. Population decoding analysis revealed that the local neuronal population in S1 encoded sufficient information to distinguish different somatosensory submodalities. Although multimodal S1 neurons responding to multiple types of stimuli exhibited no spatial clustering, S1 neurons preferring mechanical and thermal stimuli tended to show local clustering. These findings demonstrated the coding scheme of different submodalities of somatosensation in S1, paving the way for a deeper understanding of the processing and integration of multimodal somatosensory information in the cortex.

Making decisions based on knowledge about causal environmental structures is a hallmark of higher cognition in mammalian brains. Despite mounting work in psychological and cognitive sciences, how the brain implements knowledge-based decision-making at neuronal circuit level remains a terra incognita. Here we established an inference-based auditory categorization task, where mice performed within-session re-categorization of stimuli by inferring the changing task rules. Using a belief-state reinforcement learning (BS-RL) model, we quantified the hidden variable associated with task knowledge. Using simultaneous two-photon population imaging and projection-specific optogenetics, we found that a subpopulation of auditory cortex (ACx) neurons encoded the hidden task-rule variable, which depended on the feedback input from orbitofrontal cortex (OFC). Chemogenetic silencing of the OFC-ACx projection specifically disrupted re-categorization performance. Finally, imaging from OFC axons within ACx revealed task state-related value signals in line with the modeled updating mechanism. Our results provide a cortical circuit mechanism underlying inference-based decision-making.

Multiple cortical areas including primary somatosensory cortex (S1) are activated during itch signal processing, yet cortical representation of itch perception remains unknown. Using a novel miniature two-photon microscopic imaging in free-moving mice, we investigated the coding of itch perception in S1. We found that pharmacological inactivation of S1 abolished itch-induced scratching behavior, and the itch-induced scratching behavior could be well predicted by the activity of a fraction of layer 2/3 pyramidal neurons, suggesting that a subpopulation of S1 pyramidal neurons encoded itch perception, as indicated by immediate subsequent scratching behaviors. With a newly-established optogenetics-based paradigm that allows precisely-controlled pruritic stimulation, we found that a small fraction of S1 neurons exhibited ignition-like pattern at the detection threshold of itch perception. Our study revealed the neural mechanism underlying itch perceptual coding in S1, thus paving the way for studying cortical representation of itch perception at the single-neuron level in freely moving animals.