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

项目概要： 脑节律产生于有组织的神经元网络中的活动的时间协调，但是， 尖峰活动的节律协调促进大脑中信息处理的程度并不 很好理解。内侧颞叶（MTL），一个对学习很重要的相互连接的结构系统 和记忆，表现出高度动态的节奏与独特的振荡频率存在于不同的 行为状态虽然在描述单细胞和节律性细胞方面已经取得了很大的进展， MTL结构中学习和记忆的相关性，相对较少的研究考察这些之间的相互作用 现象。通过研究MTL细胞在行为过程中如何参与周围的节律回路， 运用减少或加强这种接触的方法，我们可以确定通过何种机制， 节奏协调调节MTL结构之间的通信，内部的局部信息处理 结构和学习记忆功能。拟议的项目将研究如何节奏输入从 外侧内嗅皮层（LEC）影响海马下游亚区的加工， 在情境引导的气味关联任务中的表现。通过结合使用大型神经网络， 记录和电刺激，该项目旨在1）描述LEC中的节律活动， 海马亚区在联想记忆任务期间和2）修改内源性节律活动， LEC测试是否有节奏的LEC输入足以使下游海马神经元参与任务- 有助于学习的相关活动。使用四极管和高密度硅探针的组合， 将从LEC以及树突和体细胞获得单细胞和局部场电位记录。 海马齿状回、CA 3和CA 1亚区的层。在特定目标1中，皮质和 在每个亚区中对节律性活动的内在海马影响将通过执行电流来识别。 源密度分析和将电流源和电流汇定位到远端或近端树突区域， 分别应用的概率模型也将被用来确定在多大程度上节奏的动态， LEC和每个子区域预测其他连接区域的生理反应。在具体目标2中， 交流电流刺激将用于在气味关联任务期间诱导LEC中的节律。这 aim将测试节奏输入是否足以使海马体参与有意义的节奏处理 and improve改善learning学习.该项目的结果将最终使新的治疗途径的发展 旨在改善节奏协调以缓解记忆缺陷。

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.