The representation and modulation of sensory information in the learning and memory center of the Drosophila brain

果蝇大脑学习记忆中心感觉信息的表示和调制

• 批准号: 10314793
• 负责人: Andrew M Davidson
• 金额: $ 7.1万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314793
• 关键词: Affect; Animals; Arts; Axon; BRAIN initiative; Biological; Brain; Calcium; Cells; Complex; Cues; Data; Development; Drosophila genus; Electron Microscopy; Electrophysiology (science); Environment; Functional Imaging; Generations; Genetic; Goals; Image; Individual; Insecta; Intervention; Label; Laboratories; Learning; Link; Lobe; Memory; Modeling; Motor; Mushroom Bodies; Nervous system structure; Neurons; Neurosciences; North Carolina; Odors; Output; Pathway interactions; Physiological; Physiology; Population; Positive Valence; Predisposition; Presynaptic Terminals; Process; Psyche structure; Punishment; Research; Resources; Rewards; Role; Science; Sensory; Shapes; Signal Transduction; Smell Perception; Source; Structure; Study models; Synapses; Synaptic plasticity; Technical Expertise; Techniques; Testing; Training; Training Support; Universities; Visualization; base; body sense; brain cell; career; cell type; classical conditioning; collaborative environment; college; connectome; dopaminergic neuron; experimental study; extracellular; fly; gene therapy; in vivo; medical schools; neuronal cell body; next generation; optogenetics; presynaptic; response; sensory stimulus; stimulus processing; tool

The brain uses the combined physiology of many cells to transform incoming sensory signals into internal representations. This process is critical for the animal’s survival because it underlies the animal’s ability to identify environmental cues and associate them with the condition of their situation. While sensory representation at the somatic level is well-studied, exploration of this phenomenon at the synaptic level is lacking. This is a significant gap in our understanding because individual presynaptic boutons of a single axon can be modulated independently, and this variability likely affects learning and memory. Therefore, the objective of this proposal is to expand the mechanistic understanding of the generation of a sensory signal at the presynaptic level and evaluate its role in learning-related synaptic plasticity. Preliminary data suggests that this representational activity may be variably tuned at the presynaptic level along a single axon. Based on this, the hypothesis of this proposal is that representational presynaptic activity is subject to local modulation that shapes an individual synapse’s susceptibility to plasticity. A fitting model for studying this phenomenon is that of olfactory processing in Drosophila. Olfactory information is relayed to Kenyon cells (KCs) within the mushroom body (MB), the learning and memory center of the insect brain. With a focus on individual KC axonal boutons, this proposal will explore synaptic representation and subsequent learning-induced plasticity by pursuing the following aims: (1) Analyze representational activity at the synaptic and somatic levels. (2) Determine the origin of local presynaptic modulation. (3) Evaluate the link between presynaptic representational activity and susceptibility to synaptic plasticity. This will be achieved using in vivo functional imaging and electrophysiology to study the odor response at the presynaptic and somatic levels, respectively, and using cell type-specific manipulations of potential sources of axoaxonic modulation, recently identified by the MB connectome. Completion of this project will further reveal how the nervous system represents sensory information and modulates that information during learning. This will contribute to the BRAIN Initiative’s long-term goal of understanding how sensory information gives rise to higher-order processes, like learning and sensorimotor integration. This is accomplished by using “synthetic strategies” that cross levels of biological hierarchy (from synapse to cell to circuit) to pursue the Initiative’s near- term goal of observing the brain in action using genetic tools that enable visualization and intervention. The proposal also bolsters the training of the next generation of neuroscientists by expanding the applicant’s technical expertise and promoting the applicant’s intellectual development by supporting training in a rigorous and collaborative environment that is led by a team of qualified advisors with diverse expertise. The sponsor’s laboratory is situated at the interface of the University of North Carolina’s School of Medicine and College of Arts and Sciences, and it is well-connected to the many Drosophila and neuroscience groups in North Carolina’s Research Triangle, equipping the applicant with abundant resources for preparing for an independent career.

大脑使用多个细胞的组合生理学来将传入的感觉信号转换为内部 申述。这一过程对动物的生存至关重要，因为它奠定了动物识别能力的基础 环境线索，并将它们与他们所处的情况联系起来。当感官表现在 体细胞水平已经得到了很好的研究，但在突触水平上对这一现象的探索还很少。这是一个意义重大的 我们理解上的差距，因为单个轴突的单个突触前突触可以被调制 这种可变性很可能会影响学习和记忆。因此，这项提议的目标是 为了扩大对在突触前水平产生感觉信号的机制的理解， 评估其在学习相关突触可塑性中的作用。初步数据显示，这种表象活动 可以沿着单个轴突在突触前水平进行可变调节。在此基础上，这一建议的假设 具象性的突触前活动受制于局部调制，而局部调制塑造了单个突触的 对可塑性的敏感性。一个适合研究这一现象的模型是嗅觉加工模型 果蝇。嗅觉信息被传递到蘑菇体(MB)内的凯尼恩细胞(KCs)，学习 和昆虫大脑的记忆中心。以单个KC轴突为研究对象，本提案将探讨 突触表征与后续学习诱导的可塑性：(1)分析 突触和躯体水平的表征活动。(2)确定局部突触前的起源 调制。(3)评估突触前表征活动与突触易感性之间的联系 可塑性。这将使用体内功能成像和电生理学来研究气味反应 分别在突触前和躯体水平，并使用特定细胞类型的潜力操纵 轴突调制的来源，最近由MB连接体发现。该项目的完成将进一步 揭示神经系统如何表达感觉信息，并在学习过程中调节这些信息。 这将有助于大脑计划的长期目标，即了解感官信息是如何产生的 到更高阶的过程，比如学习和感应器运动整合。这是通过使用“合成”来实现的 跨越生物层级(从突触到细胞再到回路)的战略，以追求该倡议的近 学期目标是使用基因工具观察大脑的活动，从而实现可视化和干预。这个 该提案还通过扩大申请者的技术能力来支持对下一代神经科学家的培训 专业知识和促进申请人的智力发展，通过支持在严格和 由具有不同专业知识的合格顾问团队领导的协作环境。赞助商的 实验室位于北卡罗来纳大学医学院和艺术学院的交界处 和科学，它与北卡罗来纳州的许多果蝇和神经科学团体有很好的联系 研究三角，为申请者准备独立的职业生涯提供充足的资源。