Role of GABAergic inhibitory interneurons in the emergence of environmental representations in the mouse dentate gyrus

GABA能抑制性中间神经元在小鼠齿状回环境表征出现中的作用

• 批准号: 507722788
• 负责人: Professorin Dr. Marlene Bartos
• 金额: --
• 依托单位: Lehrstuhl für Physiologie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/507722788?language=en
• 关键词: Role; GABAergic; inhibitory; interneurons; emergence

Representations of spatial environments in hippocampal networks are fundamental building blocks to the narrative of our lives. They allow us to rapidly and flexibly respond to changes within our environment. Although hippocampal principal cell (PC) assemblies have been shown to encode unique experienced environments and their re-activation is thought to reinstate the associated memory, the role of GABAergic inhibitory interneurons (INs) in the formation and stabilization of spatial representations is largely unknown. In the proposed project, (1) we aim to address this fundamental question by recording the activity of hippocampal PC and IN populations at high spatial and temporal resolution using 2-photon calcium imaging in head-fixed mice navigating through virtual environments and learn to obtain goal-oriented rewards. (2) We aim to modulate IN activity using pharmaco- and/or optogenetic tools to examine their influence on spatial representation by PC assemblies. (3) We will develop based on our established computational network models, theories on circuit mechanisms underlying the spatial and contextual representation in the dentate gyrus (DG), as the input gate of the hippocampus. A large body of work has previously identified a high diversity of morphologically, physiologically and neurochemically distinct hippocampal IN types. We will therefore focus the proposed project on examining the role of parvalbumin (PV)-expressing perisomatic-inhibitory and somatostatin (SOM)-positive distal dendrite-inhibiting INs (PVIs, SOMIs, respectively) in the DG, which is functionally vital for spatial and contextual representation in the hippocampus. Thus, our major goal is to examine how IN types influence the activity dynamics of individual PCs and PC assemblies representing a given environment in the DG. This project will contribute to our understanding on the role of IN types in the representation and encoding of environmental information and the differentiation between environments.

海马网络中空间环境的表征是我们生活叙事的基本组成部分。它们使我们能够快速灵活地应对环境中的变化。虽然海马主细胞（PC）组件已被证明编码独特的经验环境，它们的重新激活被认为是恢复相关的记忆，GABA能抑制性中间神经元（IN）在空间表征的形成和稳定中的作用在很大程度上是未知的。在拟议的项目中，（1）我们的目标是解决这个基本问题，通过记录海马PC和IN群体的活动，在高空间和时间分辨率使用双光子钙成像在头部固定的小鼠导航通过虚拟环境，并学习获得目标导向的奖励。(2)我们的目标是使用药理学和/或光遗传学工具来调节IN活性，以检查它们对PC组件空间表征的影响。(3)我们将发展基于我们建立的计算网络模型，在齿状回（DG）的空间和上下文表示的电路机制的理论，作为海马的输入门。大量的工作已经确定了高度多样性的形态学，生理学和神经化学不同的海马IN类型。因此，我们将重点研究的作用，小清蛋白（PV）表达的perisomatic抑制和生长抑素（SOM）阳性的远端树突抑制的神经元（PVIs，SOMIs，分别）在DG，这是在海马体的空间和上下文表示功能上至关重要的拟议项目。因此，我们的主要目标是研究IN类型如何影响代表DG中给定环境的单个PC和PC组件的活动动态。该项目将有助于我们理解IN类型在环境信息的表示和编码以及环境之间的区分中的作用。