Postrhinal interactions with the hippocampus in context-guided behavior

上下文引导行为中鼻后与海马的相互作用

• 批准号: 9764138
• 负责人: Valerie J. Estela-Pro
• 金额: $ 4.6万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764138
• 关键词: Address; Alzheimer' s Disease; Area; Association Learning; Behavior; Behavioral; Brain; Calcium; Cells; Characteristics; Code; Cognition; Complement; Complex Analysis; Coupled; Coupling; Custom; Data; Data Set; Decision Making; Discrimination; Disease; Educational workshop; Electrophysiology (science); Episodic memory; Event; Exhibits; Foundations; Frequencies; Goals; Hippocampus (Brain); Homologous Gene; Human; Image; Image Analysis; Imaging Techniques; Implant; Knowledge; Laboratories; Learning; Life; Literature; Location; Medial; Memory; Mental Depression; Mentors; Methodology; Methods; Mus; Neurons; Neurosciences; Patients; Perception; Performance; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Primates; Process; Rattus; Rest; Rodent; Schizophrenia; Signal Transduction; Temporal Lobe; Time; Training; Work; base; career; classical conditioning; cognitive process; density; design; developmental disease; experimental study; forging; in vivo; in vivo calcium imaging; in vivo imaging; nervous system disorder; neural circuit; neuropsychiatric disorder; new technology; novel; optical imaging; single cell analysis; skills; targeted treatment; tool

PROJECT SUMMARY Episodic memory, or the recollection of events in time and space, requires the ability to fully represent and recall context. Context-dependent cognitive processes are disrupted in a number of neuropsychiatric and neurological disorders such as schizophrenia, depression, PTSD, and Alzheimer’s disease. These disruptions are associated with changes to the parahippocampal region of the medial temporal lobe, specifically the parahippocampal cortex (PHC, human homologue of the rodent postrhinal cortex, POR) and the hippocampus (HC). The contribution of each of these areas and the mechanisms underlying the representation of these context-dependent memories is still unknown. Rebecca Burwell’s laboratory has shown that the POR, situated upstream of the HC, has neurons that respond to a particular item only when it is in a particular location (Furtak, Ahmed, and Burwell, 2012). In the HC, this type of object-location conjunctive coding emerges with the learning of an association (Komorowski, et al., 2009), and is proposed to be a signature of episodic memory. The temporal characteristics of these conjunction cells in the POR have yet to be defined, and the relationship between the conjunction cells in the POR and the HC has also not yet been described. Aim 1 of this proposal outlines the work the candidate, Valerie Estela, has accomplished to date using in vivo electrophysiology in rats to elucidate these characteristics and relationships. In order to make direct comparisons, it is necessary to record from both regions using the same task. So far only POR cells have been analyzed from rats performing a novel location biconditional discrimination task (locBCD). Briefly, it was found that 36% of POR cells exhibited object location conjunctive coding in the locBCD task, compared with 31% in the HC in a similar task (Komorowski, et al., 2009). Additional analyses and recordings from POR and HC are underway. Aim 2 of this proposal provides a detailed description of the experiments to be performed during the rest of the candidate’s dissertation. New technology will be used to record simultaneously in the POR and HC in order to examine the temporal characteristics of object-location conjunctive coding in the POR and HC during learning in the locBCD task. This method will allow for the within-subject comparison of timing of the emergence of these conjunctions as well as allowing for complex analysis of coupled rhythms, cross-frequency coupling, spike-field coherence, and ensemble analyses. To facilitate this analysis, the candidate will be trained in analytic and computational skills through one-on-one training, courses, workshops, and interactions with computational neuroscientists. Aim 3 outlines a thorough plan for finding a postdoctoral mentor specializing in cutting-edge calcium imaging techniques. This proposal has been designed to combine the candidate’s expertise in in vivo electrophysiology, in vivo calcium imaging, and the analysis of these large electrophysiology and imaging datasets to prepare the candidate for an independent career where she plans to study network level analyses of the parahippocampal cortex with the goal of understanding how neural circuits encode context to guide behavior and cognition.

项目概要 情景记忆，或者说对时间和空间中的事件的回忆，需要有能力充分再现和描述 回忆上下文。背景依赖的认知过程在许多神经精神和疾病中被破坏。 神经系统疾病，如精神分裂症、抑郁症、创伤后应激障碍和阿尔茨海默病。这些干扰 与内侧颞叶海马旁区域的变化有关，特别是 海马旁皮质（PHC，啮齿动物后鼻皮质的人类同源物，POR）和海马 （HC）。每个领域的贡献以及代表这些领域的机制 上下文相关的记忆仍然未知。丽贝卡·伯韦尔 (Rebecca Burwell) 的实验室表明，POR 位于 HC 上游，具有仅当特定项目位于特定位置时才对其做出响应的神经元 （Furtak、Ahmed 和 Burwell，2012）。在 HC 中，这种类型的对象位置联合编码随着 关联学习（Komorowski 等，2009），并被提议作为情景记忆的签名。 POR 中这些合取单元的时间特性尚未定义，并且它们之间的关系 POR 和 HC 中的连接单元之间的关系也尚未描述。本提案的目标 1 概述了候选人 Valerie Estela 迄今为止使用体内电生理学在以下领域所完成的工作： 老鼠来阐明这些特征和关系。为了进行直接比较，需要 使用同一任务从两个区域进行记录。到目前为止，仅对大鼠的 POR 细胞进行了分析 一种新颖的位置双条件辨别任务（locBCD）。简而言之，我们发现 36% 的 POR 细胞 在 locBCD 任务中表现出物体位置联合编码，而在类似任务中 HC 中表现出 31% （科莫罗夫斯基等，2009）。 POR 和 HC 的其他分析和记录正在进行中。这个目标2 提案提供了候选人剩余时间内要进行的实验的详细描述 论文。新技术将用于在 POR 和 HC 中同时记录，以便检查 locBCD 学习期间 POR 和 HC 中对象位置联合编码的时间特征 任务。该方法将允许在受试者内比较这些连词出现的时间 以及允许对耦合节律、跨频耦合、尖峰场相干性进行复杂分析， 和集成分析。为了促进这种分析，候选人将接受分析和计算方面的培训 通过一对一的培训、课程、研讨会以及与计算神经科学家的互动来培养技能。 目标 3 概述了寻找专门从事尖端钙成像的博士后导师的全面计划 技术。该提案旨在结合候选人在体内电生理学方面的专业知识， 体内钙成像，以及对这些大型电生理学和成像数据集的分析，以准备 独立职业候选人，她计划研究海马旁体的网络水平分析 皮层的目标是了解神经回路如何编码上下文以指导行为和认知。