Research Project 1 - Internal state dynamics of perception and motivati0n Lead: Karl Deisseroth MD PhD Summary This project is focused on development and application of technology for probing the interaction of external sensory input with internal states of the mammalian brain. The unique leverage of our team is technology-driven experimental access to new regimes of speed, scope, and resolution in defining and tuning these internal states. First, we will quantify the population dynamics and statistical structure of time-varying spontaneous activity across the volume of primary visual cortex (with individual cells defined by position and wiring in 3D space, and by molecular identity) to test impact of spontaneous fluctuations on environmental stimulus-triggered neuronal activity and animal behavior. Next, we will quantify cortical activity during transitions among internal states (along with behaviors), impose precisely-defined ensemble activity to assess impact of state transitions on evoked population dynamics and behavior, and quantify endogenous activity influencing these states to assess natural mechanisms and effects. Finally, we will integrate our biological findings and new technological capabilities to directly and precisely impose more complex temporal dynamics of interest by controlling multiple single cells in multiple cortical regions over time. The same cells observed to be active and important in behavior will be made available for molecular phenotyping analysis, so that cell typology may be linked to the specific natural and causal roles of cells in this important domain of circuit computation and behavior.