Optical tools to probe neural circuits in the echolocating bat

用于探测回声定位蝙蝠神经回路的光学工具

• 批准号: 10053600
• 负责人: Kishore V Kuchibhotla
• 金额: $ 70.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10053600
• 关键词: 3-Dimensional; Acoustics; Adaptive Behaviors; Affect; Animals; Arizona; Auditory area; Automobile Driving; Behavior; Behavior Control; Behavioral; Behavioral Assay; Biological Assay; Biological Models; Brain; Calcium; Cells; Chiroptera; Code; Comparative Study; Complex; Development; Devices; Dissection; Echolocation; Enhancers; Environment; Feedback; Flying body movement; Foundations; Goals; Head; Human; Image; Imaging Techniques; Implant; Inferior Colliculus; Insecta; Intercept; Interneurons; Investigation; Knowledge; Laboratory Research; Light; Location; Magnetism; Maps; Mediating; Methods; Midbrain structure; Modeling; Molecular; Monitor; Motor; Movement; Natural Selections; Neurons; Neurosciences; Neurosciences Research; Optics; Pattern; Phase; Population; Positioning Attribute; Property; Research; Research Personnel; Rodent; Role; Sensory; Signal Transduction; Specificity; Stimulus; Study models; System; Techniques; Technology; Testing; Time; Viral; Viral Vector; Virus; Wireless Technology; Work; active control; awake; base; calmodulin-dependent protein kinase II; cell type; comparative; design; experimental study; fly; neural circuit; neural network; optogenetics; promoter; relating to nervous system; response; sensory feedback; sensory input; signal processing; sonar; sound; stimulus processing; success; superior colliculus Corpora quadrigemina; tool; two-photon; vocalization

PROJECT SUMMARY/ABSTRACT: A major goal in neuroscience is to dissect the neural circuits that support complex behaviors. Comparative approaches are fundamental to the success of this goal, to separate species specializations from general principles, and to understand the brain in light of its evolved functions. The optical tools that have revolutionized circuit neuroscience in rodents must be expanded to investigate a broad range of species. Here, we propose to develop technologies to map out bottom‐up and top‐down sensory circuits in the echolocating bat, an animal that has been an important tool for furthering our understanding how the brain operates under natural conditions. The bat uses active sensing for its goal directed hunting behaviors to adapt its sonar signal design to search, track and intercept targets in the 3D environment. Here, we will optimize molecular and optical tools to determine how bottom‐up and top‐down circuits control both long‐time scale behavioral mode switching and short time‐scale behavioral adaptation. With these efforts we will also enable a wide‐range of new experiments that exploit molecular tools for circuit dissection in the echolocating bat. Initially, our focus will be on the midbrain superior colliculus (SC). The SC is critical for stimulus selection in humans and other animals, as well as for converting sensory information about the relative location of an object into motor commands for orienting. In the bat, the SC is adapted for acoustic orienting, and is therefore important to the animal's natural target search, tracking, and interception behaviors. The SC is an integrative hub receiving bottom‐up sensory input from the inferior colliculus (IC) and top‐down projections from the auditory cortex (AC). In past studies, we found that neurons in the bat SC select for natural sounds over artificial stimuli. We then pioneered recordings from the SC of behaving bats and found dynamic sensory and motor coding when behavior was adapted to track and select targets. In our proposed work, we will test the hypothesis that the IC‐AC‐SC circuit is critical for both switching between behavioral modes (e.g. search, tracking, and interception), as well as fine‐scale motor adjustments based upon sensory feedback within a behavioral mode. This type of circuit dissection requires the use of optical tools that are currently unavailable in the bat and whose development is the focus of this R34. Specifically, we propose the development of calcium imaging techniques to assay broad circuit activation, and optogenetics for cell‐specific manipulations of circuit‐level activity. To pursue these lines of investigation, we first established the feasibility of different viral tools to target cell types and circuits in the bat. We are now using our optimized AAV system to validate the applicability of two‐photon calcium imaging for monitoring neural networks in bats, with a longer‐term goal of showing how optogenetics can be used to make causal inferences about the role of different circuit components in behavioral mode switching and adaptive behavioral control. Finally, we will develop the tools to enable the use of wireless, battery free optogenetic stimulation devices to alter circuit properties in bats engaged in natural behaviors in the real, 3D environment. Through these efforts, we will be well positioned to subsequently pursue a Targeted Brain Circuits Projects R01 to dissect neural circuits supporting adaptive sensorimotor behaviors through comparative studies of rodents and bats.

项目概要/摘要： 神经科学的一个主要目标是剖析支持复杂行为的神经回路。比较 将物种专业化与一般原则分开的方法是实现这一目标的基础，并且 根据大脑的进化功能来了解大脑。彻底改变电路神经科学的光学工具 必须扩大啮齿类动物的范围以研究更广泛的物种。在这里，我们建议开发技术来绘制地图 回声定位蝙蝠中自下而上和自上而下的感觉回路，这种动物一直是人类的重要工具 进一步了解大脑在自然条件下如何运作。蝙蝠利用主动传感来实现其目标 定向狩猎行为，以适应其声纳信号设计，以在 3D 环境中搜索、跟踪和拦截目标。 在这里，我们将优化分子和光学工具，以确定自下而上和自上而下的电路如何控制两者 长时尺度的行为模式切换和短时尺度的行为适应。通过这些努力，我们还将 实现了利用分子工具对回声定位蝙蝠进行电路解剖的广泛新实验。 最初，我们的重点将放在中脑上丘（SC）上。 SC 对于人类的刺激选择至关重要 和其他动物，以及将有关物体相对位置的感官信息转换为运动 用于定向的命令。在蝙蝠中，SC 适合声学定向，因此对于动物的听觉定位非常重要 自然的目标搜索、跟踪和拦截行为。 SC 是一个集成的中心，接收自下而上的感官 来自下丘（IC）的输入和来自听觉皮层（AC）的自上而下的投射。在过去的研究中，我们发现 蝙蝠 SC 中的神经元会选择自然声音而不是人工刺激。然后我们开创了 SC 的录音 研究蝙蝠的行为，并发现当行为适应跟踪和选择目标时，动态的感觉和运动编码。在 在我们提出的工作中，我们将测试以下假设：IC-AC-SC 电路对于行为之间的切换至关重要 模式（例如搜索、跟踪和拦截），以及基于感觉反馈的精细运动调整 在一种行为模式内。这种类型的电路解剖需要使用当前无法使用的光学工具 蝙蝠的开发是这款 R34 的重点。具体来说，我们建议开发钙成像 检测广泛的电路激活的技术，以及用于电路水平活动的细胞特异性操作的光遗传学。 为了进行这些研究，我们首先确定了不同病毒工具针对目标细胞类型的可行性 和蝙蝠中的电路。我们现在正在使用我们优化的 AAV 系统来验证双光子钙的适用性 用于监测蝙蝠神经网络的成像，长期目标是展示如何使用光遗传学 对不同电路组件在行为模式切换和自适应中的作用进行因果推断 行为控制。最后，我们将开发工具来实现无线、无电池光遗传学刺激的使用 改变蝙蝠在真实 3D 环境中自然行为的电路特性的设备。通过这些 经过努力，我们将有能力随后开展目标脑回路项目 R01 来剖析神经回路 通过对啮齿动物和蝙蝠的比较研究来支持适应性感觉运动行为。