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

社会记忆下突触可塑性的输入特异性成像和操纵

• 批准号: 10163915
• 负责人: Mary L Phillips
• 金额: $ 7.36万
• 依托单位: MAX PLANCK FLORIDA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163915
• 关键词: Acute; Address; Animals; Assessment tool; BRAIN initiative; Behavior; Behavioral; Biochemical; Biological Assay; Biological Response Modifiers; Biophysics; Brain region; Computer Vision Systems; Conceptions; Cyclic AMP-Dependent Protein Kinases; Dependence; Development; Dorsal; Electrophysiology (science); Ensure; Fellowship; Florida; Goals; Hela Cells; Hippocampus (Brain); Image; Imaging Techniques; Impairment; Implant; Individual; Influentials; Institutes; Investigation; Learning; Light; Link; Memory; Mentors; Molecular; Mus; Nerve Degeneration; Neurobiology; Neurons; Neurosciences; Pathway interactions; Phosphotransferases; Presynaptic Terminals; Protein Inhibition; Protein Kinase A Inhibitor; Resources; Role; Shapes; Site; Slice; Social Behavior; Social Characteristics; Social Dominance; Social Interaction; Specificity; Synapses; Synaptic plasticity; System; Techniques; Testing; Training; Virus; Work; base; behavioral phenotyping; behavioral response; calmodulin-dependent protein kinase II; cohort; collaborative environment; commune; experience; fluorescence lifetime imaging; hippocampal pyramidal neuron; in vivo; inhibitor/antagonist; innovation; link protein; loss of function; neural circuit; neuropsychiatric disorder; neuroregulation; neurotransmitter release; novel; optical fiber; postsynaptic; presynaptic; protein kinase inhibitor; relating to nervous system; screening; sensor; social; social learning; tool; two-photon

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.

项目总结/摘要 确定行为的神经基础一直是神经生物学概念的基石目标。 虽然活动记录和功能丧失的研究已经揭示了参与和必要的大脑区域， 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， 学习和记忆的细胞关联。突触功能强度的连接变化 行为已经开始表明哪些信息回路负责编码。为了提供直接证据， 需要一种能够在行为期间调节特定电路节点中的突触可塑性的工具。 这项提议的目标是创造一种突触前可塑性的光激活抑制剂， 特定区域用于动物行为。该提案的第一个目标是创建和筛选 光活化PKI（paPKI）抑制蛋白激酶A的功效， 诱发突触前可塑性。将确保光依赖性，并将根据 使用先进的成像技术（双光子荧光寿命成像） 和生化分析。该提案的第二个目的是使用paPKI来确定特定电路的作用 社会记忆中的节点输入特定的可塑性调制将与深入的行为分析配对 利用计算机视觉来解析社会互动中的细微差异。这些目标直接针对大脑 倡议2025高优先级目标#4：使用先进的行为读数调节神经活动 计算机视觉技术 拟议的研究金项目提供了极好的培训潜力，因为它从申请人目前的 从系统/电路神经科学到分子和生物物理神经科学的培训。该项目是一个交叉点 导师安田良平博士在突触可塑性的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合作的环境，充满了该领域的领导者， 特殊的资源，导致一个机构，是非常有成效和影响力。这个奖学金申请 具有出色的培训潜力，旨在开发推动该领域发展的工具。