We will focus on the basal ganglia (BG), which are a group of subcortical nuclei thought to be vital for decision making. The BG receive extensive cortical input that carries information about the environment, which converges with dense dopaminergic input providing information about rewards. The BG regulate behavior via projections to the thalamus and brainstem, which project back to cortex, making cortico-subcortical loops. This anatomical organization means that the BG is well situated to integrate information relevant for economic choice. How value information is transformed across this circuit, and what feedback is provided to cortex by the BG is largely unknown, however. To address this gap, we will combine our naturalistic decision-making paradigm with imaging, and optogenetic and chemogenetic manipulation of genetically identified BG and cortical neurons to reveal how cortico-BG loops process value and support economic decision-making. Aim 1: Determine how cost and benefit influence foraging decisions in mice. I hypothesize that mice will adjust their choices based on the abundance of the environment such that they will be more likely to select lower value offers in “poor” blocks compared to “rich” blocks. Because cost, benefit and environmental value vary independently, and because offers are presented sequentially, this task allows unprecedented insight into the way distinct components of value influence choice and neural activity. Aim 2: Determine how the direct and indirect pathways in the striatum support foraging decisions. . To test the causal role of these populations on economic choice, depending on whether dMSNs and iMSNs comprise distinct functional groups, we will express opsins based on genetic cell type or activity-dependent immediate early gene expression. Aim 3: Discover how value information is transformed across cortico-BG loops. . To understand how value information from dMSNs and iMSNs is combined in the BG circuit, we will inhibit each pathway in the DMS while imaging in the substantia nigra (SNr), one of the output nuclei of the BG. Ultimately, this work will significantly advance our understanding of the neural circuit-level mechanisms underlying complex, value-based decision-making.
|Effective start/end date||7/1/22 → 6/30/25|
- Whitehall Foundation, Inc. (2022-05-040)
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