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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.

经典条件反射已经在许多不同的动物模型中进行了研究，甚至在人类中也是如此。但具有透明大脑的幼斑马鱼提供了一个独特的机会来观察大规模的变化，伴随这种学习形式突触结构。因此，我们开发了一种新的范例，在斑马鱼幼鱼经典条件反射过程中发生的突触变化的可视化。使用这种模式，我们已经观察到突触分布的显著区域特异性变化，这些变化驱动神经元的重新布线。介导威胁反应的电路。在这项资助中，我们将通过监测神经元活动通过成像的遗传编码的钙指示剂整个paldalphine（同系物的杏仁核）之前，期间和之后的经典条件反射和灭绝。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它们的连接。我们将研究不同的感觉输入如何引起这些细胞活动的变化，从而导致突触变化，以及联想记忆的形成或消失。这些研究的一个关键组成部分将是记录场电位以捕捉整个软腭和高速SPIM的节律性活动对基因编码的电压指示器进行成像，以记录单个细胞中的节律。通过了解精确的信号时间，冲击个别细胞，我们将揭示机制，可塑性我们的目标是开发一个理论模型，描述威胁检测的神经回路以及它们如何随着联想记忆的形成和消失而改变。