Investigating the impact of rhythmic cortical inputs upon associative memory processing in the hippocampus

研究节律性皮层输入对海马联想记忆处理的影响

基本信息

批准号：
9979531
负责人：
Lara Maria Rangel
金额：
$ 15.77万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2023-03-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY: Brain rhythms arise from the temporal coordination of activity in organized networks of neurons, but the extent to which the rhythmic coordination of spiking activity facilitates information processing in the brain is not well understood. The medial temporal lobe (MTL), a system of interconnected structures important for learning and memory, exhibits highly dynamic rhythms with unique oscillatory frequencies present during distinct behavioral states. Although great advances have been made in describing both single cell and rhythmic correlates of learning and memory in MTL structures, relatively few studies examine the interaction of these phenomena. By studying how MTL cells engage in their surrounding rhythmic circuits during behavior and applying methods to reduce or enhance this engagement, we can ascertain the mechanisms through which rhythmic coordination mediates communication between MTL structures, local information processing within structures, and learning and memory function. The proposed project will examine how rhythmic input from the lateral entorhinal cortex (LEC) influences processing in downstream subregions of the hippocampus and performance in a context-guided odor association task. Through the combined use of large-scale neural recordings and electrical stimulation, this project aims to 1) characterize rhythmic activity in the LEC and each hippocampal subregion during an associative memory task and 2) modify endogenous rhythmic activity in the LEC to test whether rhythmic LEC input is sufficient to engage downstream hippocampal neurons in task- relevant activity that facilitates learning. Using a combination of tetrodes and high-density silicon probes, both single cell and local field potential recordings will be acquired from the LEC as well as the dendritic and somatic layers of the dentate gyrus, CA3, and CA1 subregions of the hippocampus. In Specific Aim 1, cortical and intrinsic hippocampal influences upon rhythmic activity in each subregion will be identified by performing current source density analysis and localizing current sources and sinks to the distal or proximal dendritic regions, respectively. Applied probability models will also be used to determine the extent to which rhythmic dynamics in LEC and each subregion predict the physiological responses of other connected regions. In Specific Aim 2, alternating current stimulation will be used to induce rhythms in the LEC during and odor association task. This aim will test whether rhythmic inputs are sufficient to engage the hippocampus in meaningful rhythmic processing and improve learning. The results of this project will ultimately enable the development of new treatment avenues that target improvements in rhythmic coordination to alleviate memory deficits.

项目摘要：脑节律是由有组织的神经元网络中活动的时间协调引起的，但是峰值活动的节奏协调促进大脑中信息处理的程度不是理解。内侧颞叶（MTL），一种相互联系的结构系统，对学习很重要和记忆，表现出高度动态的节奏，并具有独特的振荡频率行为状态。尽管在描述单细胞和节奏方面取得了巨大进步 MTL结构中学习和记忆的相关性，相对较少的研究研究了这些相互作用现象。通过研究MTL细胞在行为过程中如何参与周围的节奏电路应用方法来减少或增强这种参与，我们可以确定有节奏的协调介导MTL结构之间的沟通，内部本地信息处理结构以及学习和记忆功能。拟议的项目将研究如何从外侧内肾上腺皮质（LEC）影响海马和海马下游区域的加工在上下文引导的气味关联任务中的性能。通过大规模神经的联合使用记录和电刺激，该项目的目的是1）表征LEC中的节奏活动关联记忆任务期间的海马次区域，2）修改内源性节奏活动测试节奏LEC输入是否足以使下游海马神经元参与任务 - 相关的活动，促进学习。使用四极管和高密度硅探针的组合，两者都将从LEC以及树突和躯体中获取单细胞和局部野外记录海马的齿状回，Ca3和Ca1子区域的层。在特定目标1中，皮质和将通过执行电流来识别每个子区域中对节奏活性的内在海马影响源密度分析并将电流源和凹陷定位到远端或近端树突状区域，分别。应用概率模型还将用于确定在多大程度上 LEC和每个子区域都预测了其他连接区域的生理反应。在特定的目标2中，交替的电流刺激将用于在气味关联任务中诱导LEC中的节奏。这 AIM将测试节奏的输入是否足以让海马参与有意义的节奏处理并改善学习。该项目的结果最终将使新的治疗途径的发展节奏协调的目标改善以减轻记忆缺陷。