Subicular Contributions to Memory-Guided Decision Making

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PROJECT SUMMARY The ability to form and store memories from experience to shape future behavior is a remarkable and foundational cognitive capability. While many brain regions interact to enable cognitive processes of learning and decision making, the subiculum and hippocampus of the medial temporal lobe are central nodes in the underlying neural circuit. Accordingly, medial temporal lobe dysfunction is a hallmark of psychiatric disorders such as depression, PTSD and other anxiety disorders, epilepsy, and Alzheimer’s disease. Understanding basic neural function and coordination processes in the subiculum and hippocampus during memory and decision making will therefore be crucial in the progress towards effective interventions for these disorders; however, subiculum function and its coordination with hippocampus during these cognitive tasks is almost completely unknown. The central hypothesis of this proposal is that subiculum links individual memories formed by the hippocampus and thereby enables cognitive capabilities such as abstraction, categorization, and deliberation during decision making. During the mentored phase (K99), high-density in vivo electrophysiology will be used in rats to observe subiculum and hippocampal subregion CA1 activity during a navigational memory-guided decision making task. Optogenetic interruption of the proposed coordination mechanism between subiculum and CA1 during behavior will then provide evidence to its necessity for memory-guided decision making. Theoretical models will assess plausible mechanisms underlying the formation of subiculum activity patterns. Experiments during the independent (R00) phase will extend this approach through the dorsal-ventral extent of CA1 and subiculum and to emotional aspects of memory such as hedonic value. Successful completion of this proposal has the potential to result in two significant conceptual breakthroughs: 1) subiculum is a major and critical component of hippocampal output with specific and distinct functions during memory-guided decision making, 2) subiculum and CA1 function and encoding properties are consistent throughout their dorsal-ventral extents and are best understood under a single conceptual framework. This research plan will be executed by Dr. Jacob Olson under the guidance of Dr. Shantanu Jadhav and Dr. Donald Katz, facilitated by the collaborative, innovative, and rigorous nature of the Neuroscience Program and Department of Psychology at Brandeis University. This proposal also contains a comprehensive training and development plan with emphases on cutting-edge recoding and manipulation techniques, theoretical modeling, and scholarly development to fully prepare Dr. Olson to lead an innovative and impactful research program studying the mechanisms of neural coordination underlying memory-guided decision making as an independent investigator.