The Neural Mechanism of Interval Timing in Drosophila

项目摘要 没有专门的感觉器官来记录时间，然而我们的大脑能够利用时间来预测 环境和适应。以秒到分钟为尺度的间隔计时过程是进化的 广泛存在，是关键的认知任务和行为的核心，包括如何以最佳方式寻找食物。尽管 这种能力的重要性，目前还没有已知的神经机制来进行这种规模的间隔计时 有机体。关于间隔计时的神经机制的问题仍然存在，部分原因是大多数 研究只记录了一个或一小部分大脑区域的神经活动。因此，要确定 间隔计时的神经机制需要全脑成像和神经元活动操纵 识别电路中的每个神经元及其作用。总的来说，这些技术是极其困难的 脊椎动物的大脑。相比之下，果蝇是推进间隔时间场的理想生物，因为它们 紧凑的大脑和容易的基因操作使全脑成像和精确的神经元扰动成为可能 以及行为分析。这项提议旨在利用果蝇和尖端技术来实现 从对时间的估计到行为的确定时间间隔的神经机制的目标 输出。这个项目的中心假设是，一个分布在整个大脑中的协调网络 估计时间，这个估计可以用来指导行为。第一个目标是检验间隔时间间隔的假设 果蝇的计时是使用整个脑区神经元网络的动态放电速率变化来编码的 大脑。第二个目的是测试果蝇使用间隔计时来估计食物密度的假设，这一点 信息与其他线索整合在一起，以改变行为。这些目标将使用行为工具来完成 分析、全脑神经活动成像和基因技术。在这个项目中获得的信息 将为任何动物的分布式计时电路提供第一个演示和机械上的理解。

Project Summary There is no dedicated sensory organ for time, and yet our brains are able to use time to anticipate the environment and adapt. The process of interval timing on a seconds to minutes scale is evolutionarily widespread and is central to critical cognitive tasks and behaviors, including how to optimally find food. Despite the importance of this ability, there is no known neural mechanism for interval timing on this scale in any organism. Questions about the neural mechanism of interval timing remain, in part, because a majority of studies record neural activity from only one or a small subset of brain regions. Therefore, to determine the neural mechanism of interval timing requires whole brain imaging and neuronal activity manipulations to identify each neuron in the circuit and their roles. These techniques are extremely difficult in the large vertebrate brain. In contrast, Drosophila are the ideal organism to advance the interval timing field as their compact brains and easy genetic manipulability allow whole brain imaging and precise neuronal perturbations as well as behavioral analysis. This proposal aims to use Drosophila and cutting-edge technologies to achieve the goal of determining the neural mechanism of interval timing from the estimation of time to behavioral output. The central hypothesis for this project is that a coordinated network distributed throughout the brain estimates time and that estimate can be used to guide behavior. The first aim tests the hypothesis that interval timing in Drosophila is encoded using dynamic firing rate changes of a network of neurons throughout the brain. The second aim tests the hypothesis that Drosophila use interval timing to estimate food density and this information is integrated with other cues to alter behavior. These aims will be completed using behavioral assays, whole-brain neuronal activity imaging, and genetic techniques. The information obtained in this project will provide the first demonstration and mechanistic understanding of a distributed timing circuit in any animal.