Imaging circuit structure and memories in a multifunctional network

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“回溯干扰”。“这不是简单的遗忘，而是后来的记忆对早期记忆的积极破坏。这个项目的核心假设是，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自然结果。在这个项目中，我们将研究两个记忆，存储在一个单一的网络中的实验有利的海洋软体动物Tritonia diomedea。使用快速电压敏感染料从神经元群体的光学记录，从单个神经元的细胞内记录与尖锐的电极，和动物的记忆存储网络的现实网络模拟的工具，我们将测试几个细胞水平的假设，在一个真实的大脑中的个人和多个记忆的解剖和功能组织。该项目将利用我们设计的一种新型混合显微镜，以促进传统的锐利电极电生理学与网络活动的大规模光学记录的整合。我们的具体目标是：目标1。扩大我们对Tritonia记忆存储逃避游泳网络的了解，包括新发现的一类“随意参与”神经元的作用。在这里，我们将描述在我们的光学记录中发现的几个新的神经元，并测试一组关于网络功能的假设。目标2.映射第一个记忆（敏化）。虽然记忆已经在突触和分子水平上得到了深入的研究，但对其在神经系统中的解剖组织了解较少。编码单一记忆的细胞和突触变化分布如何？信息的不同组成部分是如何根据记忆中可塑性的分布部位进行组织的？我们将通过绘制特里托尼亚大脑中的致敏记忆来评估有关这些问题的相互竞争的假设。目标3。映射第二记忆（习惯化），并确定它如何部分干扰，以及部分与预先存在的记忆共存。基于行为研究，习惯化似乎干扰了Tritonia中初始敏化记忆的一些但不是全部成分。在这里，我们将绘制习惯化记忆的发展过程，并试图确定它是否确实消除了先前的记忆，或者该记忆是否仍然存在，完好无损但隐藏在同一个神经网络中。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，如慢性焦虑，创伤后应激障碍和脑损伤后记忆功能障碍。公共卫生相关性：该项目研究行为功能和记忆在大脑中以分布式重叠方式组织的程度。这个重要但却鲜为人知的组织结构与各种现象都有关联，从受伤后大脑功能的恢复机制，到追溯性干扰，即后来的经历不知不觉地改变了我们先前存在的记忆。这项调查是可能的，我们开发了一种新的技术方法，在一个简单的模型准备成像大规模的网络活动。

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.