Mechanisms of perceptual decision-making in premotor cortex (360G-Wellcome-217211_Z_19_Z)

Decisions require integration of sensory evidence and prior knowledge before committing to a chosen action, but the neural mechanisms of decision-making remain poorly understood, partly because they involve the interaction of multiple brain structures and timescales. We have developed a change-detection task in mice, which separates covert antecedents of choices from motor-execution-related activity, to probe mechanisms of decision-making. Pilot data reveal that secondary motor cortex (MOs) is selectively and persistently activated by behaviourally-relevant sensory evidence when animals expect a stimulus change, and is the earliest cortical area recruited prior to executing a behavioural choice. We will determine how neural dynamics in MOs unfold as mice commit to a decision, map these dynamics on genetically and anatomically identified populations of neurons, and test their necessity for behaviour. We will identify how MOs representations are updated by sensory evidence and how this is influenced by temporal expectation. We will test specific hypothesis about circuit mechanisms that drive decision-related dynamics in MOs, using targeted optogenetic inactivations of multiple brain regions to assess their impact on behaviour. This work will identify the contribution of cortical and subcortical pathways to transforming sensory evidence into decision, and how temporal expectation influences this transformation.