Space-time processing in the hippocampus; behavioral paradigms and functional mechanism of integration

海马体的时空处理；

基本信息

批准号：
10198669
负责人：
William D Marks
金额：
$ 6.86万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
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：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10198669
关键词：
Alzheimer&apos s Disease Apical Attention deficit hyperactivity disorder Automobile Driving Behavior Behavioral Behavioral Paradigm Brain Calcium Cell Maintenance Cell physiology Cells Cues Data Decision Making Dendrites Dependence Development Discrimination Distal Episodic memory Event Exposure to Fiber Fire - disasters Fright Generations Head Hippocampus (Brain)Image In Vitro Institution Investigation Laboratories Learning Length Maintenance Medical center Memory Microscope Modality Movement Mus Nose Pattern Phase Population Process Pyramidal Cells Research Rewards Role Route Schizophrenia Signal Transduction Specificity Stream Synapses Techniques Testing Time Training Validation arm base cell type data integration data streams dentate gyrus design entorhinal cortex experience experimental study in vivo calcium imaging insight memory recall nervous system disorder novel optogenetics recruit skills time use

项目摘要

Project Summary Episodic memory is the unique recollection of a specific event in time, requiring the processing and integration of multiple information types, including spatial context and temporal information. While numerous studies on the processing of space and time as separate events have been undertaken, the understanding of the mechanisms underlying temporal processing are limited. Additionally, the means by which these information streams are integrated to form a singular memory are poorly understood. Previous research demonstrates that the hippocampus has the capability to integrate multiple spatially bound inputs with relevant contextual and nonspatial information into a singular representation. The mechanism for this integrative event as it relates to space and time is likely found more specifically within the CA1 subfield, as a discrete input carrying temporal information from entorhinal cortex layer III synapses onto the distal segments of the apical dendrites of CA1 pyramidal cells, while contextual information from EC layer II is routed through the Dentate Gyrus and CA3 before synapsing onto the proximal segments of the CA1 pyramidal cell apical dendrites. To better understand the processes underlying temporal processing, and to test whether this circuit has integrative function in episodic memory, we propose first to develop nose-poke based timing tasks for use with in-vivo calcium imaging in freely moving mice. These tasks will allow for a more refined time cell metric, give insight into the temporal encoding process, and provide a means for optogenetic investigation of circuit components with concurrent imaging of time cells. Utilizing this capability, we will optogenetically investigate the role of MECIII inputs to CA1 on time cell function and maintenance. The role of context in time cell functionality will be examined with a held nose-poke test, in which mice are trained to maintain a nose poke for a set period across multiple contexts while passive recordings of CA1 calcium activity are taken across multiple context presentations. In the final phase of this project, we will utilize cell-type specific optogenetic manipulation to inhibit terminals projecting to CA1 from ECIII or CA3 to gain a more mechanistic understanding of the integration mechanism and context dependency in time cell activity. This project will give novel insight into the mechanisms underlying episodic memory formation, temporal encoding, and how time is integrated with other data in the brain. This project will be performed at UT Southwestern Medical Center, a top tier research institution with a large variety of institutional support available. The training plan is designed to increase the applicant’s skills in in-vitro techniques, optogenetics, and behavior while also developing the applicant’s skills in presentation, grantsmanship, and laboratory management.

项目概要情景记忆是对特定时间事件的独特回忆，需要处理和整合多种信息类型，包括空间上下文和时间信息，同时还有大量研究。将空间和时间作为单独的事件进行处理，对机制的理解此外，这些信息流的底层时间处理方式也受到限制。以前的研究表明，人们对整合形成单一记忆知之甚少。海马体有能力将多个空间限制的输入与相关的上下文和信息整合起来将非空间信息转化为单一表示的机制。空间和时间可能更具体地在 CA1 子字段中找到，作为携带时间的离散输入来自内嗅皮层 III 层突触的信息到 CA1 顶端树突的远端节段锥体细胞，而来自 EC 第二层的上下文信息通过齿状回和 CA3 在突触到 CA1 锥体细胞顶端树突的近端之前时间处理的过程，并测试该电路是否具有情景积分功能记忆，我们建议首先开发基于鼻子戳的计时任务，以便自由地与体内钙成像一起使用这些任务将允许更精细的时间单元度量，深入了解时间编码。过程，并提供一种对电路元件进行光遗传学研究的方法，同时对利用时间细胞的这种能力，我们将通过光遗传学研究 CA1 的 MECIII 输入对时间细胞的作用。环境在时间细胞功能中的作用将通过鼻子戳来检查。测试，其中训练小鼠在多个环境中保持被动的鼻子戳一段时间 CA1 钙活动的记录是在多个背景演示中进行的。项目中，我们将利用细胞类型特异性光遗传学操作来抑制从 ECIII 投射到 CA1 的末端或 CA3 以便及时获得对集成机制和上下文依赖关系的更机械的理解该项目将为情景记忆形成的机制提供新的见解，时间编码，以及时间如何与大脑中的其他数据集成。该项目将在 UT 进行。西南医学中心是一家顶级研究机构，拥有多种机构支持。培训计划旨在提高申请人在体外技术、光遗传学和行为方面的技能同时还培养申请人在演讲、资助和实验室管理方面的技能。