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

单感觉和多感觉环境中行为变异性的神经机制

• 批准号: 10715471
• 负责人: Mirna Mihovilovic Skanata
• 金额: $ 28.1万
• 依托单位: SYRACUSE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-16 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715471
• 关键词: Affect; Animals; Attention deficit hyperactivity disorder; Behavior; Behavioral; Behavioral Assay; Brain; Central Nervous System; Cerebral hemisphere; Complex; Decision Making; Defect; Disease; Drosophila genus; Dyslexia; Environment; Ethics; Genetic; Human; Information Theory; Insecta; Language; Larva; Measures; Mental disorders; Microscope; Modeling; Motor Activity; Motor Neurons; Movement; Nervous System; Neurons; Optics; Organ; Organism; Process; Reagent; Research; Role; Schizophrenia; Sensory; Stimulus; Techniques; autism spectrum disorder; behavior prediction; behavioral outcome; conflict resolution; in vivo; information processing; multisensory; nervous system disorder; neural; neural circuit; neuromechanism; optogenetics; phrases; reconstruction; response; sensory input; sensory integration; two-photon

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.

项目概要/摘要 动物根据多感官输入做出的决定对它的生存至关重要。神经回路是如何 在接收多个可变输入的同时，解决在可用行为中进行选择的冲突？的 果蝇幼虫的导航行为形成了一个很有前途的模型，其中涉及神经活动和行为。 在果蝇中，强大的遗传试剂可以靶向几乎任意的10，000个神经元子集， 构成了幼虫的中枢神经系统（大脑半球约有3000个）， 网络几乎已经完成。幼虫的角质层是半透明的，其代表性昆虫的全部 大脑是光学可接近的，用于体内询问或操纵。 即使是像幼虫这样简单的有机体，对看似相同的刺激也会产生不同的反应。是什么 这种变异性的起源？这个问题可以用信息论的语言来表述。如果我反复 呈现相同的刺激并观察不同的行为，则刺激不包含完整的信息 关于行为。但是直接测量控制运动的运动神经元的活动， 总是允许一个人预测行为;这些神经元比现在有更多的关于行为的信息 这些额外的信息来源于神经系统的某个地方。 要找到幼虫易驾驭的神经系统中的变异性起源于何处以及如何起源， 描述行为的方法，识别涉及哪些神经元，解决电路活动如何编码 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定，以及有史以来第一个双光子跟踪 一种显微镜，可以记录幼虫自由导航其感觉环境时的神经活动。 在这个项目中，我将解码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， 和多动症，多感官信息的处理受到损害，可能是由于神经系统的异常， 负责整合感觉信息的回路。这项研究将促进我们对 多感官决策的神经基础，这将使我们能够更好地了解缺陷， 疾病期间发生的信息处理。