Retrosplenial representations of space and hippocampal circuitry underlying reorientation

重新定向的空间和海马回路的压后表征

• 批准号: 10362540
• 负责人: Celia Mika Gagliardi
• 金额: $ 4.04万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362540
• 关键词: Address; Affect; Alzheimer' s Disease; Animals; Architecture; Area; Behavior; Brain; Calcium; Cells; Clinical; Cognitive; Cues; Data; Dissociation; Electrophysiology (science); Environment; Event; Exposure to; Fellowship; Fiber Optics; Geometry; Goals; Head; Hippocampal Formation; Hippocampus (Brain); Image; Impairment; Implant; Lead; Learning; Lesion; Light; Location; Maps; Measures; Mus; Neurodegenerative Disorders; Opsin; Pathway interactions; Pattern; Physiologic pulse; Plants; Population; Process; Property; Reporting; Research; Rewards; Rogaine; Role; Rotation; Shapes; Surface; Testing; Texture; Therapeutic; Time; Training; Transgenic Mice; Viral; Visual; Visuospatial; behavioral impairment; cell cortex; cell type; experimental study; in vivo; in vivo calcium imaging; neural circuit; neuromechanism; optogenetics; promoter; skills; sound; spatial memory

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.

项目概要/摘要 重新定向是迷失方向时恢复方位的导航过程，对于生存至关重要，并且 由于可航行空间的表面布局往往是稳定的，因此会受到多种神经退行性疾病的影响。 时间，迷路的导航员最初使用环境的几何形状来重新定向，尽管存在定向 信息性特征线索，例如视觉地标、声音和/或纹理。然而，几何策略。 导致几何等效位置出现错误（例如，矩形的对角）。 暴露于重新定向环境中，迷失的导航者形成特征线索和目标位置的关联，以及 海马体在空间记忆中的作用已得到证实， 它的细胞整合了环境的几何和特征线索在重新定向期间，这些细胞对齐。 然而，目前尚不清楚海马体如何调节相对显着性。 当动物学习特征线索的方向价值时，它们会在重新定向过程中获取几何和特征信息。 压后皮层 (RSC) 是一个视觉空间处理区域，用于评估地标稳定性，这是一种固有的稳定性 环境几何的属性，并包含对位置、边界和头部做出响应的单元 此外，RSC 对于环境学习和损伤非常重要。 此外，RSC 还受到 GABA 能的单突触、长程抑制。 海马 CA1 区的细胞，这种投影可能有助于在重新定向过程中抑制几何形状的使用 一旦特征线索的关联形成，该提案的目标是调查环境是如何形成的。 RSC 中群体和单细胞水平的代表以及海马 GABA 能的功能作用 为了解决这些问题，本提案将研究三个目标：1) RSC 细胞群和单单位活动与环境几何相关吗？RSC 活动是否相关 预测重新定向行为？这将使用钙成像和 RSC 的单单位记录进行评估 2) 海马 GABA 能投射到 RSC 的活性。 与特征重新定向的行为相关吗？这将使用途径选择性钙来评估 海马 GABA 能细胞体在重新定向过程中投射到 RSC 的成像 3) 是否激活。 海马 GABA 能投射到 RSC 会损害几何重新定向的行为吗？ 在重新定向过程中使用 RSC 中海马 GABA 能末端的途径选择性光遗传学激活。 根据该奖学金，申请人将继续进行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还将加强她的计算和分析技能。 从多个角度解决研究问题。 重新定位将提供有关导航认知架构的关键信息。