Retrosplenial representations of space and hippocampal circuitry underlying reorientation

项目总结/摘要 重新定位，即在迷失方向时重新找到方向的导航过程，对生存至关重要， 在几种神经退行性疾病中受损。由于可航行空间的表面布局往往在 时间，迷失的导航员最初使用环境的几何形状来重新定向，尽管存在方向性 信息特征线索，例如视觉地标、声音和/或纹理。然而，几何策略 导致几何上等效位置的误差（例如，矩形的对角）。对一再发生 暴露于重新定位的背景下，迷失的导航者形成了特征线索和目标位置的关联， 重定向由特征引导。海马体在空间记忆中的作用是公认的， 它的细胞整合了环境的几何和特征线索。在重定向过程中，这些细胞会对齐 to the geometry几何of the environment环境.然而，海马体是如何调节相对显著性的， 在动物学习特征线索的方向价值的过程中，几何和特征信息的重新定位。 压后皮质（RSC）是一个视觉空间处理区域，用于评估界标稳定性， 环境几何的属性，并包含响应于地点，边界和头部的单元格， 在水平面上的方向。此外，RSC对于环境学习和损伤是重要的。 区域损害重新定向。此外，RSC接受GABA能单突触长距离抑制， 海马CA 1区的细胞，这是一个可能在重定向过程中抑制几何形状使用的突起 一旦特征线索的关联形成。本提案的目标是调查环境如何 在群体和单细胞水平上在RSC中的表达以及海马GABA能的功能作用 在重新定位期间向RSC投影。为了解决这些问题，本提案将探讨三个目标：1） RSC细胞群和单细胞活动是否与环境几何学相关，RSC活动是否与环境几何学相关， 预测再定向行为这将使用钙成像和RSC的单单位记录进行评估 细胞在重新定向过程中自由移动的小鼠。2)海马GABA能向RSC投射的活性 与特征重定向的行为相关吗这将使用路径选择性钙- 在重定向过程中投射到RSC的海马GABA能细胞体的成像。3)是否激活 海马GABA能投射到RSC损害几何重定向行为？这将被评估 使用在重新定向期间RSC中海马GABA能末端的通路选择性光遗传学激活。 在该奖学金下，申请人将继续接受体内电生理学和钙成像方面的培训， 磨练她的实验技能申请人还将加强她的计算和分析能力 从多个角度解决研究问题。阐明神经机制， 重新定位将提供有关导航认知架构的关键信息。

Project Summary/Abstract Reorientation, the navigational process of regaining one’s bearings when lost, is critical for survival and is impaired in several neurodegenerative diseases. Since surface layouts of navigable space tend to be stable over time, lost navigators initially use the geometry of the environment to reorient, despite the presence of directionally informative featural cues, such as visual landmarks, sounds, and/or textures. However, geometric strategies lead to errors in geometrically equivalent locations (e.g., opposite corners of a rectangle). Over repeated exposures to a reorientation context, lost navigators form associations of featural cues and a goal-location, and reorientation becomes guided by features. The hippocampus is well-established for its role in spatial memory, and its cells integrate both geometric and featural cues of the environment. During reorientation, these cells align to the geometry of the environment. However, it is unclear how the hippocampus modulates the relative salience of geometric and featural information during reorientation as animals learn the directional value of featural cues. The retrosplenial cortex (RSC) is a visuospatial processing region that evaluates landmark stability, an inherent property of environmental geometry, and contains cells that are responsive to places, borders, and head- direction on the horizontal plane. Moreover, the RSC is important for environmental learning and lesions to this area impair reorientation. Additionally, the RSC receives monosynaptic, long-range inhibition from GABAergic cells in hippocampal area CA1, a projection that may serve to inhibit the use of geometry during reorientation once associations of featural cues are formed. The goal of this proposal is to investigate how environments are represented in the RSC at the population and single-cell level and the functional role of hippocampal GABAergic projections to RSC during reorientation. To address these questions, this proposal will investigate three aims: 1) Are RSC cell population and single-unit activities correlated with environmental geometry and does RSC activity predict reorientation behavior? This will be assessed using calcium-imaging and single-unit recordings of RSC cells in freely moving mice during reorientation. 2) Does activity of hippocampal GABAergic projections to RSC correlate with behavior in reorientation by features? This will be assessed using pathway-selective calcium- imaging of hippocampal GABAergic cell bodies projecting to RSC during reorientation. 3) Does activation of hippocampal GABAergic projections to RSC impair behavior in reorientation by geometry? This will be assessed using pathway-selective optogenetic activation of hippocampal GABAergic terminals in RSC during reorientation. Under this fellowship, the applicant will continue her training in in vivo electrophysiology and calcium-imaging, honing her skills as an experimentalist. The applicant will also strengthen her computational and analytical skills to address research questions from multiple perspectives. Elucidation of neural mechanisms underlying reorientation will provide critical information about navigational cognitive architecture.