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: 10436182
• 负责人: Andrew M Davidson
• 金额: $ 7.26万
• 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/10436182
• 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.

大脑利用许多细胞的综合生理学将传入的感觉信号转化为内部信号 交涉。这个过程对于动物的生存至关重要，因为它是动物识别能力的基础 环境线索并将其与自身处境条件联系起来。虽然感官表征 体细胞水平已得到充分研究，但缺乏对突触水平这种现象的探索。这是一个意义重大的 我们的理解存在差距，因为单个轴突的各个突触前按钮可以调节 独立地，这种可变性可能会影响学习和记忆。因此，本提案的目标是 扩大对突触前水平感觉信号产生机制的理解 评估其在学习相关突触可塑性中的作用。初步数据表明，这种代表性活动 可以沿着单个轴突在突触前水平进行可变调节。基于此，本提案的假设 代表性的突触前活动受到局部调节，从而塑造了单个突触的 对可塑性的敏感性。研究这种现象的一个合适模型是嗅觉处理模型 果蝇。嗅觉信息被传递到蘑菇体 (MB) 内的凯尼恩细胞 (KC)，学习 和昆虫大脑的记忆中枢。该提案重点关注单个 KC 轴突纽扣，将探讨 通过追求以下目标来研究突触表征和随后的学习诱导的可塑性：（1）分析 突触和体细胞水平的代表性活动。 (2)确定局部突触前起源 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。这将通过体内功能成像和电生理学来研究气味反应来实现 分别在突触前和体细胞水平，并使用细胞类型特异性的电位操作 轴轴调节的来源，最近由 MB 连接组确定。该项目的完成将进一步 揭示神经系统如何表示感觉信息并在学习过程中调节该信息。 这将有助于实现大脑计划的长期目标，即了解感官信息如何产生 到更高阶的过程，如学习和感觉运动整合。这是通过使用“合成 跨生物层次结构（从突触到细胞到电路）的“策略”，以追求该计划的近期目标 术语目标是使用能够可视化和干预的遗传工具观察大脑的活动。这 该提案还通过扩大申请人的技术能力来加强对下一代神经科学家的培训 通过支持严格和严格的培训来促进申请人的专业知识和智力发展 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着密切的联系 研究三角，为申请人提供丰富的资源，为独立职业做好准备。