Tuesday, May 7, 2024
5/7/2024
PROJECT SUMMARY Interactions between the hippocampus and mesolimbic dopamine system supports memory encoding and subsequent consolidation to stabilize salient information in long-term memory. These episodic traces are used to support a variety of adaptive behaviors, including inference, generalization, and decision-making. Information seeking further represents a context in which motivated learning occurs in the absence of explicit reward, including incubation-induced craving and context-dependent feedback. In this way, information seeking may serve as a model to dissect how mesolimbic-hippocampal circuits contribute to the complexity of drug seeking behavior. Most research characterizing the contributions of mesolimbic-hippocampal interactions on memory have focused on reward. However, this circuit is also critically involved in memory enhancements resulting from active exploration. Critically, memory enhancements during active information seeking involves the integration of mesolimbic signaling across multiple elements of an event (cues versus outcomes) and timescales (event-evoked versus state-dependent). Rodent studies show that hippocampal engagement during exploration triggers a positive feedback loop, which increases tonic dopamine signaling in the ventral tegmental area (VTA), which in turn yields larger VTA anticipation and feedback responses. Prominently, these positive feedback loops could instantiate and propagate the variety of behaviors contributing to substance use. We propose to characterize how state-dependent VTA responses relate to memory enhancements during active information seeking using a combination of novel behavioral paradigms, state-of-the-art neuroimaging, and computational modeling to inform mechanisms underlying memory. Aim 1 will study mesolimbic- hippocampal contributes to memory encoding during active learning and hypothesis testing. Aim 2 will study how engagement of this circuit during encoding stabilizes memory representations during periods of post- encoding consolidation. Finally, Aim 3 will utilize a computational psychiatry approach to study how individual differences in memory during active information seeking relates to predictors of substance use risk.
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