Hippocampal-Striatal Co-operative Synergistic Interaction

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Despite the accumulating evidence demonstrating that distinct types of memory interact differently in specific circumstances, both normal and pathological, the factors modulating 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 lateral dorsal striatum (DSL). The medial DS (DSM) is involved in spatial navigation and has been linked to behavioral flexibility. Memory systems in general, and the HPC and DS memory systems in particular, are thought to operate independently and in parallel to support spatial and response learning, respectively. However, our Preliminary Data indicate that the principle of independent parallelism does not hold in all conditions. When animals concurrently learn a spatial navigation and a stimulus-response task, the two memory systems operate co-operatively and in synergy. Our long-term goal is to investigate the neurobiological basis of hippocampal and striatal contributions to behavior. The objective of the current proposal is to expand our understanding of the factors promoting the cooperative synergism mode of operation of HPC and DS memory systems. The central hypothesis of the proposed work is that proximity in space and time of two different types of learning experiences promotes the dual involvement of the corresponding memory systems in behavioral guidance regardless of other factors; in these conditions, co-operative synergism trumps independent parallelism. The rationale underlying the proposed research is that we need to characterize the factors that modulate the interaction of the two memory systems to behavior in order to understand how the HPC and DS neural circuits may combine to support normal and pathological behavior. The hypothesis will be tested by pursuing two specific aims: Identify how proximity in space and time of learning experiences contributes to cooperative synergism between HPC and DS memory systems by assessing memory deficits in rats with HPC, DSL or DSM lesions after training in a behavioral paradigm comprised of a spatial navigation and a cue response task acquired a) in close succession but in two different rooms; or b) in the same room but separated by 5-6 hour interval; 2. Investigate the generalizability of cooperative synergism by assessing the memory deficits in rats with HPC, DSL, or DSM lesions in the double task behavioral paradigm ran in an open field apparatus. The expected contribution of the proposed research is to identify the conditions in which the HPC and DS memory systems interact co- operatively and in synergism to support behavior. This contribution is significant because it leads to understanding the fundamental principles of interaction between memory circuits and the role of these principles in the process of guiding behavior. The proposed research is innovative because it investigates the DS-HPC interaction while explicitly requiring the animals to engage in two different types of learning.