Retrosplenial representations of space and hippocampal circuitry underlying reorientation

项目摘要/摘要 重新定向是迷失方向后重新找到方向的导航过程，对生存至关重要，也是 患有几种神经退行性疾病。由于可导航空间的表面布局往往稳定在 时间，迷失的导航者最初使用几何环境来重定向，尽管存在方向性 信息性特征提示，例如视觉地标、声音和/或纹理。然而，几何策略 导致在几何等价位置(例如，矩形的对角)中的误差。过度重复 暴露在重新定向的上下文中，迷路的导航员形成了特征提示和目标位置的关联，以及 重定向将由特征引导。海马体因其在空间记忆中的作用而广为人知， 它的细胞整合了环境的几何和特征线索。在重定向过程中，这些单元格对齐 与环境的几何形状有关。然而，目前还不清楚海马体如何调节相对的突出性。 随着动物学习特征线索的方向性价值，在重新定位过程中几何和特征信息的变化。 脾后皮质(RSC)是一个视觉空间处理区域，它评估标志性的稳定性，这是一种固有的 环境几何属性，并包含对位置、边界和头部做出响应的单元格- 水平面上的方向。此外，RSC对环境学习非常重要，并对此造成损害 面积会影响重定向。此外，RSC接受来自GABA能的单突触、长距离抑制 海马区CA1区的细胞，这一投影可能有助于在重定向过程中抑制几何图形的使用 一旦形成了特征线索的关联。这项提案的目标是调查环境是如何 以RSC为代表的群体和单细胞水平及海马区GABA能的功能作用 在重定向期间投影到RSC。为了解决这些问题，本提案将调查三个目标：1) RSC细胞数量和单个单位的活动是否与环境几何形状相关，以及RSC活动 预测重定向行为？这将使用钙成像和RSC的单位记录进行评估 自由移动的小鼠在重定向过程中的细胞。2)海马GABA能投射向RSC的活动 与通过特征重定向时的行为相关？这将使用途径选择性钙- 重定向过程中投射到RSC的海马GABA能细胞体的成像。3)激活 海马区GABA能投射到RSC会损害几何重定向时的行为吗？我们将对此进行评估 在重定向过程中利用通路选择性光遗传激活RSC中的海马GABA能终末。 根据这项奖学金，申请者将继续她的体内电生理学和钙成像方面的培训， 磨练她作为实验者的技能。申请者还将加强她的计算和分析技能 从多个角度解决研究问题。阐明潜在的神经机制 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.