Decision-making is an essential component of spatial navigation as animals convert environmental cues and internal signals into locomotor actions to reach goal locations. In many experimental paradigms, the neural mechanisms for navigation and decision-making have been studied separately, leaving open important questions about how these processes are linked. Findings from our previous grant period, along with recent work in the field, indicate that the dorsal, posterior cortex ? visual, parietal, and retrosplenial cortices ? participate in key computations for navigation-based decision-making. Here we propose to test working models of how these areas and their interactions contribute during navigation-based decision tasks. We will develop a range of new tools including: behavioral tasks and analyses for navigation-based decision-making in virtual reality environments, calcium imaging approaches to record activity in neuronal populations in multiple areas at cellular resolution over weeks, and computational approaches to understand the encoding of behavioral and task features in single neurons and large populations. In a first aim, we will test hypotheses about how visual, parietal, and retrosplenial cortices make distinct contributions to navigation-based decision tasks. We will use a combination of behavioral modeling, optogenetic perturbations, and calcium imaging. In a second aim, we will analyze the information transmitted between visual, parietal, and retrosplenial cortices on a moment-by-moment basis during navigation decisions. We will image activity in multiple cortical regions simultaneously and analyze information flow in conjunction with retrograde labeling approaches. In a third aim, we will address how these representations and inter-area interactions develop during learning of navigation- and decision-related associations. We will use methods to track the activity of the same neurons, in multiple cortical regions, daily over weeks as mice learn phases of navigation-based decision tasks. Together, this work will advance our understanding of how cortical regions and their interactions mediate the planning and choice computations essential for effective decision- making during spatial navigation.
The disruption of spatial navigation and decision-making contributes to many neurological disorders, including Alzheimer?s disease. The proposed experiments will reveal fundamental aspects of how cortical regions interact and change over time to mediate spatial navigation and decision-making. By using new technologies and computational tools, our results are expected to reveal insights into neural circuit functions for decision- making in health and disease.
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