Circuits underlying threat and safety

电路潜在威胁和安全

基本信息

批准号：
10218722
负责人：
DONALD B ARNOLD
金额：
$ 471.85万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10218722
关键词：
Affect Amygdaloid structure Anatomy Animal Model Animals Anxiety Architecture Area Behavior Behavioral Brain Brain region Cells Cessation of life Computer Models Computer software Control Animal Custom Data Data Analyses Data Display Detection Electrophysiology (science)Ensure Environment Excitatory Synapse Extinction (Psychology)FAIR principles Fishes Future Goals Grant Homologous Gene Human Hypothalamic structure Image Individual Inhibitory Synapse Label Lead Learning Light Location Mammals Maps Measures Mediating Membrane Potentials Memory Mental Depression Methodology Methods Microscopy Modeling Molecular Monitor Nature Neurons Optics Output Pain Periodicity Physiological Population Property Recombinants Reproducibility Research Safety Signal Transduction Speed Stimulus Structure Synapses Synaptic plasticity Tail Testing Theoretical model Time Tissues Zebrafish base biophysical model calcium indicator cell type classical conditioning conditioning data management deep learning experimental study improved neural circuit neuronal patterning neuroregulation novel optogenetics physical state response sensory input sensory stimulus signal processing voltage

项目摘要

Classical conditioning has been studied in many different animal models, and even in humans. However, the larval zebrafish with its transparent brain offers a unique opportunity to observe large scale changes in synaptic structure that accompany this form of learning. Accordingly, we have developed a novel paradigm for visualizing synaptic changes that occur during classical conditioning in larval zebrafish. Using this paradigm we have observed striking region-specific changes in the distributions of synapses that drive the rewiring of neural circuits that mediate threat responses. In this grant we will expand this paradigm by monitoring neuronal activity through imaging of genetically encoded calcium indicators throughout the pallium (the homolog of the amygdala) before, during and after classical conditioning and extinction. This will allow us to identify cells that comprise the circuits that control threat and safety and explore their connectivity using optogenetics. We will investigate how different sensory inputs can cause changes in the activity of those cells leading to synapse change, and the formation or extinction of associative memories. A crucial component of these studies will be the recording of field potentials to capture rhythmic activity throughout the pallium and high speed SPIM imaging of genetically encoded voltage indicators to record rhythms in individual cells. By understanding the precise timing of signals that impinge on individual cells we will uncover mechanisms that underlie synaptic plasticity. Our goal is to develop a theoretical model describing the neural circuits that underlie threat detection and how they can change as a result of associative memory formation and extinction.

在许多不同的动物模型，甚至在人类中都研究了经典条件。但是，幼虫斑马鱼及其透明大脑提供了一个独特的机会，可以观察到大规模变化这种学习形式的突触结构。因此，我们为可视化在幼虫斑马鱼中经典调节期间发生的突触变化。使用这个范式我们已经观察到突触驱动神经重新布线的突触分布的引人注目的区域特异性变化介导威胁响应的电路。在这笔赠款中，我们将通过监测神经元扩大此范式通过整个pallium的遗传编码钙指标的成像（通过杏仁核）在经典调节和灭绝之前，之中和之后。这将使我们能够识别细胞包括控制威胁和安全的电路，并使用光遗传学探索其连通性。我们将研究不同的感觉输入如何导致这些细胞的活性变化导致突触变化以及联想记忆的形成或灭绝。这些研究的关键组成部分将是在整个pallium和高速刺激中捕获节奏活动的田间潜能的记录遗传编码的电压指标的成像以记录单个细胞中的节奏。通过理解构成单个单元格的信号的精确时机，我们将发现突触的基础的机制可塑性。我们的目标是开发一个描述威胁检测基础的神经回路的理论模型以及它们如何随着关联内存形成和灭绝而改变。