The computational power of the human brain derives from its neuronal wiring. Neuronal circuits are the engine of the brain, for they transform simple inputs into complex outputs underlying behavior and cognition. Novel technologies are transforming the analysis of brain circuits. Research in our laboratory has combined two-photon measurements of neuronal activity and dynamics in the intact mouse brain with manipulations of activity to discover specific and unique functions of inhibitory neuron classes and their circuits in cortical response tuning and gain control. Probing mechanisms of internal states, we have demonstrated a crucial role for cholinergic inputs to inhibitory-disinhibitory circuits in shaping the temporal dynamics of cortical activity, a mechanism that underlies neuronal desynchronization and decorrelation during arousal and attention. These discoveries demonstrate that cortical circuits contribute particular functions, and even ‘diffuse’ neurotransmitter systems actvia cell‑specific circuits to modulate cortical processing and brain states. Local and long-range circuits together mediate behavior: our experiments in awake behaving mice, combining large scale imaging across multiple areas and optogenetic manipulation, have revealed principles of information flow from sensory through parietal to motor and prefrontal cortex in mice during goal-directed behavior. The logic of these circuits reveals fundamental principles of information processing underlying sensorimotor transformations, and lays the groundwork for rich experimental and computational analyses of normal and abnormal brain function. FINANCIAL SUPPORT: Supported by grants from NIH, NSF, and the Simons Foundation Autism Research Initiative
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