Molecular control of ensemble dynamics to govern remote memory precision in adult and aged mice

整体动力学的分子控制以控制成年和老年小鼠的远程记忆精度

• 批准号: 408078506
• 负责人: Dr. Hannah Twarkowski, Ph.D.
• 金额: --
• 依托单位: Sahay Lab
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/408078506?language=en
• 关键词: Molecular; control; ensemble; dynamics; govern

New memories are encoded in the hippocampus and finally stored in the neocortex. It is widely recognized that communication between the hippocampus and the cortex is important for the consolidation and precision of remote memories. Although, studies suggest synchronized neuronal firing events such as sharp-wave ripples to support hippocampal-cortical communication, the underlying circuit mechanisms are poorly understood. This is partly due to lack of tools to specifically manipulate discrete circuit elements and assess their causal roles in vivo. CA3 and CA1 inhibitory interneurons are thought to be a main source of sharp-wave ripples and dentate granule cells (DGC) connectivity with inhibitory interneurons has been suggested to positively correlate with memory precision. Here, we will leverage a recently developed molecular tool to specifically manipulate DG neuron connectivity with inhibitory interneurons with unprecedented control. In combination with longitudinal in vivo calcium imaging in behaving mice, we will test the hypothesis that increasing DG neuron recruitment of feedforward inhibition (FFI) onto CA3 promotes stabilization of neuronal representations of memories over time. Since excitation-inhibition imbalance in CA3 characterizes age-associated memory impairments, we will also assess the impact of our manipulation in aged mice. The proposed studies will illuminate how an elemental feature of the DG-CA3 circuit, namely FFI, promotes hippocampal-cortical communication and precision of long-term memories.

新的记忆在海马体中编码，最后储存在新皮层中。人们普遍认为，海马体和皮层之间的通信对于远程记忆的巩固和精确是重要的。虽然，研究表明同步神经元放电事件，如尖锐波波纹，以支持大脑皮层通信，底层电路机制知之甚少。这部分是由于缺乏专门操纵离散电路元件和评估其在体内的因果作用的工具。CA 3和CA 1抑制性中间神经元被认为是锐波波纹的主要来源，并且已经表明齿状颗粒细胞（DGC）与抑制性中间神经元的连接与记忆精度正相关。在这里，我们将利用最近开发的分子工具，专门操纵DG神经元与抑制性中间神经元的连接，具有前所未有的控制。 结合行为小鼠的纵向体内钙成像，我们将测试这一假设，即增加DG神经元对CA 3的前馈抑制（FFI）的募集，随着时间的推移，促进记忆的神经元表征的稳定。 由于CA 3中的兴奋-抑制失衡表征了与年龄相关的记忆障碍，我们还将评估我们的操作对老年小鼠的影响。 拟议的研究将阐明DG-CA 3电路的一个基本特征，即FFI，如何促进大脑皮层的通信和长期记忆的精确性。