The role of dentate gyrus interneuron plasticity in the representation of location, environment and objects

齿状回中间神经元可塑性在位置、环境和物体表征中的作用

• 批准号: 521666973
• 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/521666973?language=en
• 关键词: role; dentate; gyrus; interneuron; plasticity

How information is processed and represented in the brain to enable individual organisms to adapt behavior to their continuously changing environment is a fundamental building block of current neuroscience. However, little progress has been made on how memory traces emerge in neuronal networks during learning. Current theories propose that during learning modifications of synaptic weights enable a selected group of principal cells (PCs) to form a new cell association, which represents the new information. However, how these cell associations emerge across time and how GABAergic inhibitory interneurons may contribute to this process is largely unknown. We hypothesise that synaptic plasticity at excitatory glutamatergic inputs onto interneurons (INs) supports their recruitment and thereby markedly contribute to memory trace formation. Here, we aim to address this hypothesis on somatostatin (SOM) expressing interneurons (SOMIs) of the dentate gyrus (DG) targeting distal dendrites of local granule cells (GCs), the PCs of this brain area. We recently identified group I metabotropic glutamate receptor 1 (mGluR1) and mGluR5 as key molecular mechanisms underlying the emergence of synaptic plasticity at GC-mediated synapses onto SOMIs. (1) Here, we aim to perform whole-cell recordings in acute hippocampal slice preparations to examine the major molecular cascades downstream of mGluR1 underlying plasticity induction at GC-SOMI synapses and compare them with our already published ones for GC synapses targeting parvalbumin (PV)-expressing interneurons. (2) We aim to apply our recently tested small hairpin RNA (shRNA) interference tools for mGluR1 knockdown, to examine the impact of lost SOMI input plasticity on neuronal network dynamics. We will us 2-photon imaging in the DG of head-fixed mice navigating through a virtual reality on a liner track searching for rewards and 1-photon imaging of freely moving mice performing a DG-dependent object-recognition task. (3) We will apply population-vector based decoder analysis of population activity obtained on the linear track and during free spatial exploration to examine the impact of IN plasticity on the encoding of the current location, the environment and memorized objects. Thus, the major goal of the proposed project is to examine how SOMI plasticity influences activity dynamics of GC assemblies encoding information about space, context (where?) and objects within an environment (what?). This project will contribute to our understanding on the role of IN input plasticity in memory. We believe that this work is clinically relevant, since deficits in IN function are hallmarks of cognitive diseases.

信息如何在大脑中被处理和呈现，以使个体生物适应不断变化的环境，是当前神经科学的一个基本组成部分。然而，在学习过程中记忆痕迹如何在神经网络中出现的问题上，进展甚微。目前的理论认为，在学习过程中，突触权重的改变使一组被选择的主细胞（PCs）形成一个新的细胞协会，代表新的信息。然而，这些细胞关联如何随着时间的推移而出现，以及gaba能抑制性中间神经元如何促进这一过程，在很大程度上是未知的。我们假设兴奋性谷氨酸能输入到中间神经元（INs）的突触可塑性支持它们的募集，从而显著促进记忆痕迹的形成。在这里，我们的目的是解决这一假设，表达生长抑素（SOM）的齿状回（DG）中间神经元（SOMIs）靶向局部颗粒细胞（GCs）的远端树突，该脑区域的pc。我们最近发现I组代谢性谷氨酸受体1（mGluR1）和mGluR5是gc介导的SOMIs突触突触可塑性出现的关键分子机制。(1)在这里，我们的目标是在急性海马切片制备中进行全细胞记录，以检查mGluR1下游GC- somi突触可塑性诱导的主要分子级联，并将其与我们已经发表的针对表达小蛋白（PV）的中间神经元的GC突触进行比较。(2)我们的目标是应用我们最近测试的小发夹RNA （shRNA）干扰工具来检测mGluR1敲低，以研究SOMI输入可塑性丢失对神经网络动力学的影响。我们将研究头部固定的小鼠在线性轨道上通过虚拟现实导航寻找奖励的双光子成像和自由移动的小鼠执行依赖于DG的物体识别任务的单光子成像。(3)我们将对线性轨迹和自由空间探索过程中获得的种群活动进行基于种群向量的解码器分析，以检验IN可塑性对当前位置、环境和记忆对象编码的影响。因此，所提议的项目的主要目标是研究SOMI可塑性如何影响GC程序集的活动动态，这些程序集编码有关空间、上下文（在哪里？）和环境中的对象（什么？）的信息。这个项目将有助于我们理解IN输入可塑性在记忆中的作用。我们相信这项工作具有临床意义，因为in功能缺陷是认知疾病的标志。