Thursday, December 26, 2024
12/26/2024
PROJECT SUMMARY (ABSTRACT) The long-term goal of the proposed research is to elucidate the systems and circuits, within and across brain regions, responsible for decision making. The objective of this proposal is to determine how a single target for movement is selected among competing alternatives. An experimentally-tractable approach to achieving this objective is to interrogate neural circuitry in behaving animals engaged in deciding where to move, a particularly important form of decision making for survival that we refer to here as spatial choice. The midbrain superior colliculus (SC) integrates input from several systems representing variables critical for goal-directed behavior, topographically represents contralateral spatial targets for orienting movements, and is a critical node in the network of brain regions responsible for spatial choice. However, the mechanisms underlying how spatial choices are made is poorly understood. In a series of experiments in awake and behaving mice, we test the overall hypothesis that inhibitory SC neurons, driven by local pre-motor output, mediate spatial choice by suppressing SC populations representing competing targets. The premise for this hypothesis is supported by decades of foundational research in behaving animal models and brain slices, and by our and others’ recent work leveraging the behaving mouse model to unify these two branches of research. In particular, in the previous funding cycle we found that inhibitory SC neurons do not merely suppress local pre-motor output, but instead mediate spatial choice via long-range projections. To test our overall hypothesis, In Aim 1, we examine how activating inhibitory SC neurons modulates activity across both SCs, under baseline conditions in quiescent mice and in behaving mice performing an odor- cued spatial choice task requiring selection of a left or right reward port. We then record and perturb specific projection-based subtypes of inhibitory SC neurons during spatial choice. These experiments test the hypothesis that inhibitory SC neurons shape activity at distal sites in the SC, providing a mechanism for selecting among competing spatial goals. In Aim 2, we will determine the relationship between the activity of pre-motor SC neurons and distally-projecting inhibitory SC neurons by recording and perturbing their activity during quiescence and behavior. These experiments will test the hypothesis that pre-motor SC neurons inhibit activity in populations representing distal targets by locally activating long-range inhibitory SC neurons. If successful, the outcome of this proposal will be the elucidation of the neural circuit basis for spatial choice, a key basic function of the nervous system. In addition, our research will lay the groundwork for elucidating how SC circuitry is extrinsically modulated by other brain regions to subserve goal-directed behavior.
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