Circuits underlying threat and safety

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。

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.