Postrhinal interactions with the hippocampus in context-guided behavior

项目摘要 情景记忆，或对时间和空间中事件的回忆，需要完全再现和 回忆上下文。在许多神经精神和神经心理疾病中， 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。这些中断 与内侧颞叶海马旁区的变化有关，特别是 海马旁皮质（PHC，啮齿动物后嗅皮质的人类同源物，POR）和海马 （HC）。每个领域的贡献以及代表这些领域的机制 背景相关记忆仍然是未知的。丽贝卡·伯韦尔的实验室已经表明，位于 在HC的上游，有神经元，只有当它处于特定位置时，才会对特定的物品做出反应 （Furtak，Ahmed和Burwell，2012）。在HC中，这种类型的对象位置合取编码随着 学习关联（Komorowski，et al.，2009年），并建议作为情节记忆的签名。 POR中这些联合细胞的时间特征尚未被定义， POR和HC中的连接细胞之间的连接也尚未被描述。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完成的工作， 大鼠阐明这些特征和关系。为了进行直接比较，必须 使用相同的任务从两个区域记录。到目前为止，只有POR细胞已被分析，从大鼠执行 一种新的位置双联想辨别任务（locBCD）。简而言之，发现36%的POR细胞 在locBCD任务中显示出物体位置联合编码，而在类似任务中，HC中有31%显示出物体位置联合编码 （Komorowski等人，2009年）。POR和HC的其他分析和记录正在进行中。目标2 提案提供了在候选人的其余部分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，以检查 在locBCD中学习过程中POR和HC中对象位置联合编码的时间特性 任务这种方法将允许在受试者内比较这些连接出现的时间 以及允许对耦合节律、交叉频率耦合、尖峰场相干性 和集合分析。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，研讨会和与计算神经科学家的互动来提高技能。 目标3概述了一个彻底的计划，寻找博士后导师专门从事尖端钙成像 技术.该提案旨在将候选人在体内电生理学方面的专业知识与联合收割机相结合， 体内钙成像，并分析这些大型电生理学和成像数据集，以准备 候选人为一个独立的职业生涯，她计划研究网络水平的分析海马旁 目的是了解神经回路如何编码上下文以指导行为和认知。

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.