Physiological Mechanisms of Hippocampal-Striatal Interactions

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DESCRIPTION (provided by applicant): Despite the accumulating evidence demonstrating that distinct types of memory interact differently in specific circumstances, both normal and pathological, the neurophysiological correlates that may support these processes remain unknown. Declarative memories, which include spatial representations, are dependent on a neural network centered on the hippocampus (HPC), while habits, which include stimulus-response associations, require an intact dorsal striatum (DS). More recently, it has been shown that the medial DS (DSM) has a spatial navigation function, while the lateral DS (DSL) is responsible for cue-motor response associations. Spatial and motor learning can occur simultaneously and can exert concomitant influence on behavioral output, while also directly influencing each other. Our long-term goal is to characterize the neurophysiological substrates of HPC-DS interaction. The objective of the current proposal is to evaluate the potential contribution of DSM to HPC activity by testing whether DSM activity directly influences memory- dependent HPC activity patterns such as hippocampal journey-dependent activity (HJDA) which encodes origin and destination of journeys. Our central hypothesis is that HJDA, generated through processing of information in the local hippocampal network and encoding the where aspects of experience, combines with AC, involved in goal-directed motor output, to adequately guide overt behavior. The rationale underlying the proposed research is that once we identify the relationship between neural activities in the two memory structures, we can understand how HPC and DS neural circuits may combine to support normal and pathological behavior. The hypothesis will be tested by pursuing two specific aims: 1. Identify the role of DSM in spatial navigation in the plus maze task by assessing rats' ability to engage in spatial navigation or cue response a plus maze after temporary inactivation of DMS through bilateral muscimol infusions in the area; 2. Identify the contribution of DSM activity to HJDA by recording CA1 neural activity in rats with inactivated DSM that reacquire spatial information after hippocampal infusion of zeta inhibitory peptide (ZIP; an inhibitor of protein kinase Mζ that has been linked to memory and long-term plasticity processes). The expected contribution of the proposed research is to identify the contribution of DSM to HPC activity during spatial learning. This contribution is significant because it will reveal how the activity in two structures with distinct memory functions may combine to guide behavioral performance. The research proposed in this application is innovative because it investigates the neural substrate of HPC-DSM interaction by recording in a behavioral paradigm with established neural substrate while selectively disrupting memory-related neural firing through interference with memory-related synaptic plasticity.