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: 7869560
• 负责人: William Frost
• 金额: $ 7.7万
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7869560
• 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，人类记忆不准确。尽管新获得的记忆往往具有很高的有效性，但随着随着时间的流逝，随后的经历可能会改变或降解它们，而这种现象称为“追溯干扰”。这不是简单的忘记，而是后来记忆的积极腐败。该项目的核心假设是，记忆之间的干扰自然来自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。在这个项目中，我们将研究两个记忆，这些记忆存储在实验有利的海洋软体动物Tritonia diomedea的单个网络中。使用来自具有快速电压敏感染料的神经元群体的光学记录工具，来自具有锋利电极的单个神经元的细胞内记录以及对动物存储器网络的逼真的网络模拟，我们将测试几个细胞水平的假设，涉及有关个体的解剖学和功能性组织，以及在真实大脑中的多个记忆。该项目将利用由我们设计的新型混合显微镜，以促进传统的锋利电极电生理学与网络活动的大规模光学记录。我们的具体目的是：目标1。扩展我们对Tritonia的内存存储逃生游泳网络的了解，包括新发现的“随便参与”神经元的角色。在这里，我们将描述我们在光学录制中发现的几个新神经元，并测试有关网络功能的一组假设。 AIM 2。映射第一个内存（敏化）。尽管在突触和分子水平上对记忆进行了深入研究，但对其神经系统中的解剖组织的理解却较少。蜂窝和突触更改编码单个内存的分布方式？信息的不同组成部分如何相对于记忆的可塑性分布点？我们将通过绘制记忆以在Tritonia大脑中的敏化来评估有关这些问题的竞争假设。 AIM 3。绘制第二个内存（习惯），并确定其如何部分干扰并部分共存于敏化的已有记忆。基于行为研究，习惯似乎干扰了特里托尼亚初始敏化记忆的某些部分但并非所有组成部分。在这里，我们将随着习惯的发展而绘制记忆，并尝试确定它是否确实删除了先前的记忆，或者该记忆是否持续存在，完整但隐藏在同一神经网络中。该项目的长期目标是更好地了解大脑中记忆的网络组织，以及重叠的存储如何影响记忆准确性，其目标是为诸如慢性焦虑，创伤后应激障碍和脑损伤后的记忆力障碍等疾病开发更好的治疗方法。公共卫生相关性：该项目研究了以分布式，重叠的方式组织行为功能和记忆的程度。这种重要但知之甚少的组织计划与现象相关，从受伤后的脑功能恢复机制到追溯干扰，后来的经历如此阴险地改变了我们的先前记忆。通过在简单的模型准备中开发一种新的技术方法，可以通过开发一种新的技术方法来进行研究。