In-vivo control of information flow by artificial stimulation: ephys and behavior

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DESCRIPTION (provided by applicant): In-vivo control of information flow by artificial stimulation: ephys and behavior Sensory pathways in the brain exist to extract and process information about the outside world, so that we may perceive our environment and make decisions about our actions. In contrast to motor control, where a rich history of investigation has formed a foundation for linking neuronal population activity in motor regions to elements of motor output, we do not have an analogous general framework for providing surrogate signals to sensory pathways. Using a combination of acute and awake-behaving experiments in the rat vibrissa system, coupled with sub-cortical patterned electrical and optical (optogenetic) stimulation, voltage sensitive dye (VSD) imaging of cortical activation, ideal observer and information theoretic analyses, and precise sensory behavioral tasks, we are uniquely positioned to develop a framework for characterizing, optimizing, and controlling information flow in sensory pathways induced through artificial activation of neural structures. In this project, we will 1) utilize electrical and optical stimulation of the thalamus in conjunction with n-vivo VSD imaging in cortex of the anesthetized rat to assess the detectability and discriminability of a range of stimuli from the perspective of an ideal observer of cortical activiy, and formulate a principled basis for stimulation design for optimizing discriminability, 2) manipulate the level of thalamic depolarization/synchrony through background depolarization/hyperpolarization using optogenetic techniques to shape the nonlinear response properties of the circuit and develop control of the level of detectability and discriminability among sets of inputs, and 3) develop a behavioral framework for artificial manipulation of the trade-off between detectability and discriminability to optimize performance in different contexts. Significance: The development of artificial means by which to activate sensory circuits for impaired individuals is thus an extremely important public health issue, and the development of principles for controlling information flow in sensory pathways is of paramount importance, but currently does not exist. Furthermore, being able to activate downstream brain structures in a precise manner is also critical in the basic scientific investigation of how populations of neurons represent information and how these representations are propagated across brain regions - to understand the neural code. Innovation: The conceptual innovation here is the use of the link between performance of an ideal observer of cortical activity and behavior as a design and optimization tool for artificial stimulation. We use an innovative combination of in-vivo electrophysiology with multi-electrode, mult-site recording, voltage sensitive dye imaging, patterned microstimulation and optogenetics, highly specific behavioral tasks, and a control-theoretic framework, which together do not exist in the scientific community.