Research Unit 5159

Title: Cortexwide neural dynamics during multisensory decision-making

Short Summary: Understanding how cortical circuits dynamically integrate sensory information to generate complex behavior requires investigating the cell types that comprise them. To address this, we used widefield imaging to measure the cortex-wide activity of distinct classes of excitatory pyramidal neurons (PyNs) and investigated their functional role in mice that performed a multisensory decision-making task. We used two mouse lines, expressing the calcium indicator GCaMP6s in either pyramidal-tract (PT) or intratelencephalic (IT) neurons. We found major PyN-specific differences in the complexity and spatial layout of cortical activity patterns, at both local and mesoscale levels, suggesting the existence of specialized subcircuits. Sensory responses were largest in the sensory, parietal, and frontal cortex but each PyN type showed pronounced differences in cortical localization and spatial specificity. Additionally, choice-related activity differed between PyN types, with PT neurons displaying ramping and contralateral choice-selective activity in the frontal cortex, while IT neurons showed ipsilateral choice signals. PyN-type-specific optogenetic inhibition of the parietal cortex disrupted sensory processing, while frontal inactivation of subcortically-projecting PT neurons affected choice formation. High-density Neuropixels recordings in the frontal cortex and the superior colliculus (SC) revealed clear differences in neural coding, such as context-dependent choice signals in the frontal cortex but not the deep SC. Our work reveals PyN-specific dynamics throughout the cortex, showing that cortical regions perform parallel computations through distinct cortical-subcortical interactions that enable multisensory choice formation.