Hippocampal-Striatal Co-operative Synergistic Interaction

海马-纹状体协同相互作用

• 批准号: 9435600
• 负责人: Janina Diana Ferbinteanu
• 金额: $ 24.23万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9435600
• 关键词: Affect; Alzheimer' s Disease; Animal Experiments; Animals; Autistic Disorder; Behavior; Behavioral; Behavioral Paradigm; Biological Neural Networks; Brain; Complex; Corpus striatum structure; Cues; Data; Dimensions; Dissociation; Dorsal; Early Diagnosis; Event; Goals; Habits; Hippocampus (Brain); Hour; Huntington Disease; Investigation; Knowledge; Lateral; Learning; Length; Lesion; Link; Medial; Memory; Memory Disorders; Memory impairment; Mental Depression; Mental disorders; National Institute of Mental Health; Neurobiology; Operating System; Outcome; Output; Pathologic; Pattern; Post-Traumatic Stress Disorders; Process; Public Health; Rattus; Research; Response to stimulus physiology; Role; Schizophrenia; Structure; System; Testing; Time; Training; Work; Yin; base; behavioral response; experience; experimental study; flexibility; innovation; memory process; mental development; neural circuit; neural correlate; neuromechanism; neurotoxic; operation; relating to nervous system; response; spatiotemporal; synergism; therapy development; way finding

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.

尽管越来越多的证据表明，不同类型的记忆在特定的环境中会产生不同的相互作用， 在正常和病理的情况下，调节这些过程的因素仍然未知。 陈述性记忆，包括空间表征，依赖于一个以 海马体（HPC），而习惯，包括刺激反应协会，需要一个完整的侧 背侧纹状体（DSL）。内侧DS（DSM）参与空间导航，并与 行为灵活性一般来说，存储器系统，且特定来说，HPC及DS存储器系统， 被认为是独立和平行运作，分别支持空间和反应学习。 然而，我们的初步数据表明，独立平行的原则并不适用于所有 条件当动物同时学习空间导航和刺激反应任务时， 存储器系统协作地和协同地操作。我们的长期目标是调查 海马和纹状体对行为贡献的神经生物学基础。当前的目标 建议是扩大我们对促进合作协同运作模式的因素的理解 HPC和DS内存系统。拟议工作的中心假设是，在空间和 两种不同类型的学习经验的时间促进了相应的双重参与 记忆系统的行为指导，而不考虑其他因素;在这些条件下，合作协同作用 胜过了独立的并行性。拟议研究的基本原理是，我们需要 描述调节两个记忆系统相互作用与行为的因素，以便 了解HPC和DS神经回路如何联合收割机支持正常和病理行为。 该假设将通过追求两个具体目标进行测试：确定空间和时间上的接近程度 的学习经验有助于HPC和DS记忆之间的协同增效作用 通过评估HPC，DSL或DSM损伤大鼠在行为训练后的记忆缺陷， 一个由空间导航和线索反应任务组成的范式获得a）在紧密的连续性，但在两个 不同的房间;或B）在同一个房间，但相隔5-6小时; 2.探讨 通过评估HPC、DSL或 双任务行为范式中的DSM病变在开放领域装置中运行。预期贡献 建议的研究是确定HPC和DS存储器系统相互作用的条件， 有效地和协同地支持行为。这一贡献意义重大，因为它导致了 理解记忆电路之间相互作用的基本原理以及这些原理的作用。 指导行为过程中的原则。拟议的研究是创新的，因为它调查了 DS-HPC相互作用，同时明确要求动物参与两种不同类型的学习。