Neural mechanisms underlying behavioral variability in uni- and multi-sensory contexts

项目摘要/摘要 动物在多感官输入的基础上做出的决定对其生存至关重要。神经电路是如何 在接收多个可变输入的同时解决冲突以在可用行为中进行选择？这个 果蝇幼虫的导航行为形成了一个将神经活动和行为联系起来的有希望的模型。 在果蝇中可以使用强大的遗传试剂来靶向近10,000个神经元的任意亚群，这些神经元 组成幼虫的中枢神经系统(大脑半球约3000个)，并对其进行EM重建 网络即将完成。幼虫的角质层是半透明的，其代表昆虫的整个 大脑可以通过光学方式进行活体审问或操作。 即使是像幼虫这样的简单有机体，对看似相同的刺激表现也会做出不同的反应。是什么 这种差异的根源是什么？这个问题可以用信息论的语言来表述。如果我反复 呈现相同的刺激，观察不同的行为，那么刺激就不包含完整的信息 关于他的行为。但直接测量控制运动的运动神经元的活动将 总是允许一个人预测行为；这些神经元拥有比现在更多的关于行为的信息 在刺激中，这些额外的信息源自神经系统的某个地方。 要找出幼虫易驯服的神经系统中变异的来源和方式，这项任务需要一个完整的 描述行为、识别涉及哪些神经元、解析电路活动如何编码的方法 这些行为，并发现产生这些神经转换的机制。为了完成这项任务， 我已经开发了两种神经回路询问技术：光遗传反向相关行为 可以确定任何目标神经元在决策中的作用的测试，以及有史以来第一个双光子跟踪 当幼虫自由地在其感觉环境中导航时，可以记录神经活动的显微镜。 在这个项目中，我将破译幼虫对单感官和多感官的导航反应背后的电路 输入。在许多神经和精神疾病中，如精神分裂症、自闭症谱系障碍、阅读障碍、 和ADHD，多感官信息的处理受到影响，可能是由于神经的异常 负责整合感觉信息的回路。这项研究将增进我们对 多感官决策的神经基础，这将使我们更好地理解 疾病期间发生的信息处理。

Project summary/abstract Decisions an animal makes on the basis of multi-sensory input are crucial to its survival. How do neural circuits resolve conflicts to choose among available behaviors while receiving multiple and variable inputs? The navigational behaviors of larval Drosophila form a promising model in which to relate neural activity and behavior. Powerful genetic reagents are available in Drosophila to target nearly arbitrary subsets of 10,000 neurons that make up the larva’s central nervous system (~3, 000 in the brain hemispheres), and an EM reconstruction of this network is almost complete. The larva’s cuticle is semi-transparent, and the entirety of its representative insect brain is optically accessible for in vivo interrogation or manipulation. Even a simple organism like the larva responds variably to seemingly identical stimulus presentations. What is the origin of this variability? This question can be phrased using the language of information theory. If I repeatedly present the same stimulus and observe different behaviors, then the stimulus does not contain full information about the behavior. But directly measuring the activities of the motor neurons that control movement would always allow one to predict the behavior; these neurons have more informationabout the behavior than is present in the stimulus, and this extra information originates somewhere in the nervous system. The task of finding where and how variability originates in larva’s tractable nervous system requires an integrated approach in describing a behavior, identifying which neurons are involved, resolving how circuit activity encodes those behaviors, and discovering the mechanisms generating these neural transformations. To achieve this task, I have developed two techniques of neural circuit interrogation: an optogenetic reverse-correlation behavioral assay that can determine the role of any targeted neuron in decision making, and a first ever two-photon tracking microscope that can record the neural activity as larva freely navigates its sensory environments. In this project, I will decode the circuitry underlying the larva’s navigational responses to uni- and multi-sensory input. In many neurological and psychiatric disorders, such as schizophrenia, autism spectrum disorder, dyslexia, and ADHD, the processing of multisensory information is compromised, perhaps from abnormalities in the neural circuits that are responsible for integrating sensory information. This research will advance our understanding of the neural basis of multisensory decision-making, which will allow us to better understand the defects in information processing that occur during disease.