Imaging circuit structure and memories in a multifunctional network

多功能网络中的成像电路结构和存储器

• 批准号: 7789461
• 负责人: William Frost
• 金额: $ 30.49万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789461
• 关键词: Affect; Animals; Anxiety; Attitude; Behavior; Behavioral; Biological Neural Networks; Bite; Brain; Brain Injuries; Chronic; Chronic Post Traumatic Stress Disorder; Clinical; Collaborations; Commit; Data Set; Development; Disease; Dyes; Electrodes; Electrophysiology (science); Feeling; Functional disorder; Goals; Human; Hybrids; Image; Individual; Injury; Investigation; Knowledge; Laboratory Study; Lead; Learning; Life; Maps; Marines; Memory; Memory Disorders; Methods; Microscope; Modeling; Molecular; Motor; Nervous system structure; Neurobiology; Neurons; Optical Methods; Optics; Persons; Physiological; Physiological Processes; Play; Population; Post-Traumatic Stress Disorders; Preparation; Procedures; Recovery; Role; Running; Scheme; Site; Space Explorations; Structure; Swimming; Synapses; Techniques; Testing; Time; Training; base; calin; design; experience; fascinate; forgetting; improved; independent component analysis; innovation; insight; interest; novel; novel strategies; prevent; programs; public health relevance; research study; shared memory; simulation; tool; voltage

DESCRIPTION (provided by applicant): Human memory is notoriously inaccurate. Whereas newly acquired memories tend to have high validity, over time subsequent experiences can change or degrade them, a phenomenon termed "retroactive interference." This is not simple forgetting, but an active corruption of earlier memories by later ones. The central hypothesis of this project is that interference between memories results naturally from the brain's method of storing related information in partially overlapping fashion in neural networks. In this project we will study two memories that are stored together in a single network of the experimentally advantageous marine mollusk Tritonia diomedea. Using the tools of optical recording from neuronal populations with fast voltage-sensitive dyes, intracellular recording from individual neurons with sharp electrodes, and realistic network simulations of the animal's memory-storing network, we will test several cellular level hypotheses regarding the anatomical and functional organization of individual and multiple memories in a real brain. The project will utilize a new, hybrid microscope designed by us to facilitate the integration of conventional sharp electrode electrophysiology with large-scale optical recording of network activity. Our specific aims are: Aim 1. Expand our knowledge of Tritonia's memory-storing escape swim network, including the role of a newly-discovered class of "casually participating" neurons. Here we will characterize several new neurons discovered in our optical recordings, and test a set of hypotheses about network function. Aim 2. Map the first memory (sensitization). While memory has been intensively studied at the synaptic and molecular level, less is understood about its anatomical organization in nervous systems. How distributed are the cellular and synaptic changes encoding a single memory? How are the different components of information organized with respect to the distributed sites of plasticity underlying the memory? We will evaluate competing hypotheses regarding these issues by mapping out the memory for sensitization in the Tritonia brain. Aim 3. Map the second memory (habituation), and determine how it partially interferes with, and partially co-exists with the pre-existing memory for sensitization. Based on behavioral studies, habituation appears to interfere with some but not all components of an initial sensitization memory in Tritonia. Here we will map the memory for habituation as it develops, and will attempt to determine whether it does indeed erase the prior memory, or whether that memory persists, intact but hidden, in the same neural network. The long-term goal of this project is to better understand the network organization of memories in the brain, and how overlapping storage affects memory accuracy, with the goal of developing better treatments for conditions such as chronic anxiety, post-traumatic stress disorder, and memory dysfunction after brain injury. PUBLIC HEALTH RELEVANCE: This project investigates the degree to which behavioral functions and memories are organized in distributed, overlapping fashion in the brain. This important but poorly understood organizational scheme has relevance for phenomena ranging from mechanisms of recovery of brain function after injury, to retroactive interference, where later experiences so insidiously manage to alter our preexisting memories. This investigation is made possible by our development of a new technical approach for imaging large-scale network activity in a simple model preparation.

描述（由申请人提供）：众所周知，人类的记忆是不准确的。虽然新获得的记忆往往具有很高的有效性，但随着时间的推移，随后的经历可能会改变或降低它们，这种现象被称为“追溯干扰”。这不是简单的遗忘，而是后来的记忆对早期记忆的主动破坏。该项目的中心假设是，记忆之间的干扰是大脑在神经网络中以部分重叠的方式存储相关信息的方法自然产生的。在这个项目中，我们将研究两个存储在一起的记忆，它们存储在实验上有利的海洋软体动物 Tritonia diomedea 的单个网络中。使用具有快速电压敏感染料的神经元群体的光学记录工具、具有锋利电极的单个神经元的细胞内记录以及动物记忆存储网络的真实网络模拟，我们将测试关于解剖和功能组织的几种细胞水平假设真实大脑中的个体和多重记忆。该项目将利用我们设计的新型混合显微镜，以促进传统锐电极电生理学与网络活动的大规模光学记录的集成。我们的具体目标是： 目标 1. 扩展我们对 Tritonia 记忆存储逃生游泳网络的了解，包括新发现的一类“随意参与”神经元的作用。在这里，我们将描述在光学记录中发现的几个新神经元的特征，并测试一组有关网络功能的假设。目标 2. 映射第一个记忆（敏化）。虽然记忆在突触和分子水平上得到了深入研究，但对其在神经系统中的解剖结构了解甚少。编码单一记忆的细胞和突触变化的分布如何？信息的不同组成部分是如何根据记忆底层可塑性的分布式站点进行组织的？我们将通过绘制 Tritonia 大脑中的敏化记忆来评估有关这些问题的相互竞争的假设。目标 3. 绘制第二记忆（习惯化）图，并确定它如何部分地干扰先前存在的记忆，以及部分地与先前存在的记忆共存以实现敏化。根据行为研究，习惯化似乎会干扰 Tritonia 初始敏化记忆的部分但不是全部组成部分。在这里，我们将绘制记忆发展过程中的习惯化图谱，并尝试确定它是否确实删除了先前的记忆，或者该记忆是否完整但隐藏地持续存在于同一个神经网络中。该项目的长期目标是更好地了解大脑中记忆的网络组织，以及重叠存储如何影响记忆准确性，目标是开发更好的治疗方法，治疗慢性焦虑症、创伤后应激障碍和抑郁症等。脑损伤后记忆功能障碍。公共健康相关性：该项目研究了行为功能和记忆在大脑中以分布式、重叠的方式组织的程度。这种重要但鲜为人知的组织方案与从损伤后大脑功能恢复机制到追溯干扰等各种现象相关，其中后来的经历如此阴险地改变了我们先前存在的记忆。我们开发了一种新技术方法，可以通过简单的模型准备对大规模网络活动进行成像，从而使这项研究成为可能。