Pulvinar cellular and network dynamics in cognitive control of sensory processes.

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PROJECT 1 SUMMARY P1 is aligned with each of the Center’s 3 overarching aims: 1. Identify cognitive functional organization principles of higher order thalamic nuclei in interacting with cortex; 2. Translate thalamic functionality from animal models to healthy and diseased human brain; 3. Develop a biologically plausible model for human higher order thalamus. Specifically, P1 will investigate regions of the pulvinar associated with early visual cortical areas (V1, V2, and V4) to test specific hypotheses about cognition and circuit dynamics in higher order thalamus. This project takes advantage of the retinotopic relationship between pulvinar and cortex to enable precise electrode placement for studying the influence of cognitive control on circuit dynamics at a synaptic, cellular, and network level. In alignment with Center Aim 1, results from P1 will be compared to those from P2, P3, and P4 to establish a comprehensive and mechanistic understanding of the role of higher order thalamus in cognitive control. In alignment with Center Aim 2, results from P1 will provide a framework for understanding the impact of disease in (P5). In alignment with Center Aim 3, results from P1 will inform Core B as its models evolve. Core C will provide essential analytical tools for P1 as well as ensure that data can be exchanged and compared between projects. In P1/Aim 1, we will record from optogenetically identified regions of pulvinar associated with V1, V2, and V4 in monkeys performing the APU task. We will then optogenetically silence the V1 inputs to these PUL regions to assess their role in decision making and spatial attention. In P1/Aim 2, we will use an assay developed in our laboratory, the “dual-neuron shock-spike assay”, to determine the spatial organization of attention effects in the pulvinar and the influence of attention on the efficacy of pulvino-cortical communication. Lastly, in P1/Aim 3, we will use optogenetics to inactivate V1 and V2 axons within the pulvinar to determine the influence of cognitive factors on pulvinar regulation of cortico-cortical communication.