Subicular Contributions to Memory-Guided Decision Making

项目总结 从经验中形成和存储记忆以塑造未来行为的能力是一种非凡的和 基础认知能力。虽然许多大脑区域相互作用，使学习的认知过程 和决策，内侧颞叶的下丘脑和海马体是大脑的中央节点。 潜在的神经回路。因此，内侧颞叶功能障碍是精神障碍的标志。 如抑郁症、创伤后应激障碍和其他焦虑症、癫痫和阿尔茨海默病。了解基础知识 记忆和决策过程中下丘脑和海马区的神经功能和协调过程 因此，在为这些疾病采取有效干预措施方面取得进展至关重要；然而， 在这些认知任务中，下丘脑的功能及其与海马体的协调几乎完全 未知。这一提议的中心假设是，下丘脑连接着个体记忆，这些记忆由 海马体，从而使认知能力，如抽象，分类和审议 在决策过程中。在指导阶段(K99)，将在体内使用高密度电生理学 导航记忆引导下大鼠下丘脑和海马区CA1活性的观察 决策任务。所提出的下丘脑和下丘脑之间的协调机制的光发生中断 然后，行为过程中的CA1将提供证据，证明其对记忆引导决策的必要性。理论上的 模型将评估下丘脑下丘活动模式形成的可能机制。实验 在独立(R00)阶段，将通过CA1和CA1的背腹范围扩展该入路 下丘脑和情感方面的记忆等享乐性价值。成功完成本建议书 有可能导致两个重大的概念突破：1)下丘脑是一个主要和关键的 在记忆引导的决策过程中，具有特定和独特功能的海马体输出的组成部分， 2)下丘脑和CA1的功能和编码特性在其背腹方向上是一致的 并在单一概念框架下得到最好的理解。这项研究计划将由雅各布博士执行 奥尔森在尚塔努·贾达夫博士和唐纳德·卡茨博士的指导下，在合作的推动下， Brandeis神经科学项目和心理系的创新性和严谨性 大学。该提案还包含一项全面的培训和发展计划，重点是 尖端的记录和操作技术、理论建模和学术发展 让奥尔森博士做好准备，领导一个创新和有影响力的研究项目，研究神经的机制 作为一个独立的调查者，协调记忆引导的决策制定。

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.