Modulation of hippocampal cognitive maps by dopaminergic midbrain and prefrontal cortex

University Of Texas At Austin, Austin TX

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Abstract

PROJECT SUMMARY/ABSTRACT Memory forms not only through successful encoding of single learning instances, but also through the integration of information across collective experience. Leading memory theories suggest that events that overlap with prior experience may trigger reactivation of related memories, with new events being integrated into the reactivated memory context. Despite the broad reaching behavioral impacts of memory integration, little is known about the underlying neural mechanisms. Additionally, studies of memory integration in humans have almost solely been tested using artificial laboratory paradigms and give us little information about how experiences are formed and updated in naturalistic contexts. The research presented in this proposal will use new virtual reality paradigms in combination with functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to investigate the mechanisms of memory integration in naturalistic environments. Previous work has implicated the hippocampus and medial prefrontal cortex (mPFC) in memory integration by showing, for instance, increased engagement of these regions during encoding of overlapping events. Dopaminergic midbrain regions may also promote memory integration by innervation of hippocampus to facilitate this new encoding. A key goal of the proposed work is to determine how the hippocampus, mPFC, and midbrain representations of episodic experience are formed and updated in naturalistic contexts, resulting in an integrated cognitive map. Experiment 1 will test our key prediction using a new virtual reality task to examine whether events experienced within the same environment (1) will come to be represented similarly within the hippocampus and mPFC and (2) will be neurally separable from events experienced in different environments. Experiment 2 will build upon Experiment 1 by characterizing how a cognitive map formed through spatial learning impacts non-spatial processing. The key reasoning is that activating learned cognitive maps will facilitate processing of overlapping items, reflected by faster response times and reduced fMRI signal (i.e. enhanced repetition suppression), relative to non-overlapping items. Using resting-state data, we will also test how individual differences in connectivity among hippocampus, mPFC, and midbrain regions relate to cognitive map formation and generalization ability. Experiment 3 will build upon the virtual environment paradigm, which is the framework of Experiment 1, by parametrically manipulating the visual similarity between environments. This modification will elicit hippocampal neural patterns that vary in their integration processing based on visual similarity. Moreover, the proposed studies may provide a new means to characterize the mechanisms by which memory degradation is impacted in clinical populations, such as Alzheimer?s disease and Parkinson?s disease, which are characterized by pathological changes within the hippocampus and mPFC and behavioral deficits in memory and navigation.