The role of medial striatum in spatial sequence learning

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The hippocampus (HPC) encodes concomitantly current, past and future locations; and distinguishes between events that occur in the same place as part of distinct experiences. These aspects of HPC activity are likely to support episodic memory, which encodes personally experienced past events. However, the neural substrate that supports the use of these episodic memories to achieve flexible behavior remains insufficiently understood, precluding thus the development of treatments in memory disorders. One way in which memory- based flexible behavior may be generated is by transient coordination of activity between HPC and other local memory networks such as dorso-medial striatum (DSM) which is involved in behavioral flexibility and whose neurons fire in action-modulated manner (action choice, AC). The long-term goal of this line of research is to understand how circumstantial mnemonic demand may lead to transient functional coupling of distinct local memory circuits in order to guide behavior (the dynamic model of memory). The objective of the current proposal is to evaluate the contribution of DSM to disambiguation of repeated traversals of the same physical spatial locations while on distinct journeys (sequential context), a task relevant for HPC function and episodic memory. The central hypothesis of the current proposal is that the structure of the behavioral task modulates how similar events that occur in the same space are distinguished as part of different episodes in the HPC-DSM network. The rationale of the proposed work is that a determination of how neural circuits use stored information to act adequately in similar but yet distinct circumstances will offer a strong scientific framework whereby new strategies in memory research can be developed.. We propose the following two specific aims: Aim 1. Identify the roles of HPC and DSM activities in disambiguation of sequential contexts. The working hypothesis of this aim is that a combination of neural firing in both HPC and DSM is necessary to successfully distinguish the extended spatial sequences that share segments of trajectory. Aim 2. Identify the HPC/DSM neural activity patterns that are correlated with successful disambiguation of sequential contexts Our working hypothesis is that although HPC does not differentiate between sequential contexts at the second scale, distinction is made at the millisecond scale in place cells' activity in combination with the activity of DSM neurons which encode AC. We expect the results of the proposed research to demonstrate that that disambiguation of sequential contexts involves a neural network encompassing both HPC and DSM (Aim 1); and that analyzing the deep structure of neural activity will uncover how the HPC representation combines with DSM activity to guide behavior when appropriate action involves memory of distinct past events that occurred in the same environment (Aim 2). The results of the proposed research will contribute to fully understanding the neural basis of episodic memory, which has implications for several neurological and mental illnesses, and will lead to submission of an R01-equivalent proposal.