Input-specific imaging and manipulation of synaptic plasticity underlying social memory

项目摘要/摘要 自神经生物学概念提出以来，确定行为的神经基础一直是一个基石目标。 虽然活动记录和功能丧失研究揭示了大脑涉及的和必要的区域 某些行为的表达，他们无法确定每个电路负责的信息 编码。因此，当电路中的不同节点被移除时，行为表型通常是相同的。 突触可塑性，即突触根据经验改变功能强度的能力，被认为是 学习和记忆的细胞关联。突触功能强度的变化与以下情况有关 行为已经开始表明哪些信息电路负责编码。为了提供直接证据， 需要一种工具，能够在行为过程中调节特定电路节点的突触可塑性。 这项提议的目标是创造一种可光激活的突触前可塑性抑制物，它将被输入-和 特定地区的，用于表现动物的行为。该提案的第一个目标是创建和筛选 光激活蛋白激酶I(PaPKI)抑制蛋白激酶A的有效性 突触前可塑性的诱导。将确保对光的依赖性，并将根据以下条件对结构进行评估 用先进的成像技术研究其灵敏度和选择性(双光子荧光寿命成像) 和生化分析。该提案的第二个目标将使用PPKI来确定特定电路的作用 社会记忆中的节点。特定于输入的可塑性调节将与深入的行为分析相结合 使用计算机视觉来解析社交互动中的细微差异。这些目标直接针对大脑 计划2025高优先级目标4：通过使用高级读数来调节神经活动 计算机视觉技术。 拟议的奖学金项目提供了极好的培训潜力，因为它从申请者目前的 从系统/电路神经科学到分子和生物物理神经科学的培训。这个项目是一个交叉点 在导师安田良平博士、突触可塑性分子机制方面的专业知识和 生物调节器和传感器的开发和先进成像，以及申请人在电路方面的专业知识 使用计算机视觉进行潜在的社会记忆、电生理学和行为分析。马克斯·普朗克 佛罗里达神经科学研究所是一个高度协作的环境，充满了该领域的领导者和 超凡的资源，造就了一个生产力高、影响力大的研究所。这份奖学金提案 表现出极好的培训潜力，目标是生产出能够推动该领域发展的工具。

Project Summary / Abstract Ascertaining the neural basis of behavior has been a cornerstone goal since the conception of neurobiology. While activity recording and loss-of-function studies have shed light on brain regions involved and necessary for the expression of certain behaviors, they are unable to determine the information each circuit is responsible for encoding. Therefore, when different nodes in the circuit are removed, the behavioral phenotype is often identical. Synaptic plasticity, the ability of synapses to change functional strength depending on experience, is considered the cellular correlate of learning and memory. Linking changes in the functional strength of synapses following behavior has begun to indicate what information circuits are responsible for encoding. To provide direct evidence, a tool that is able to modulate synaptic plasticity in specific circuit nodes during behavior is needed. The goal of this proposal is to create a photo-activatable inhibitor of presynaptic plasticity that will be input- and region- specific for use in behaving animals. The first aim of the proposal will create and screen constructs of photo-activatable PKI (paPKI) in their efficacy for the inhibition of protein kinase A, a kinase necessary for the induction of presynaptic plasticity. Light-dependency will be ensured and the construct will be evaluated based on its sensitivity and selectivity using advanced imaging techniques (2-photon fluorescence lifetime imaging) and biochemical assays. The second aim of the proposal will use paPKI to determine the role of specific circuit nodes in social memory. Input-specific modulation of plasticity will be paired with in depth behavioral analyses using computer vision to parse out subtle differences in social interaction. These aims directly address the BRAIN Initiative 2025 high priority goal #4: the modulation of neural activity with readouts of behavior using advanced computer vision techniques. The proposed fellowship project provides excellent training potential as it expands from the applicant’s current training in systems/circuit neuroscience to molecular and biophysical neuroscience. The project is an intersection between the mentor’s, Dr. Ryohei Yasuda, expertise in molecular mechanisms of synaptic plasticity and the development and advanced imaging of biomodulators and sensors, and the applicant’s expertise in circuitry underlying social memory, electrophysiology and behavioral analyses using computer vision. The Max Planck Florida Institute for Neuroscience is an intensely collaborative environment filled with leaders in the field and exceptional resources, resulting in an institute that is highly productive and influential. This fellowship proposal presents excellent training potential and aims to produce tools that will advance the field.