权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

批准号：
10645081
负责人：
Andrew M Davidson
金额：
$ 7.93万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/10645081
关键词：
Affect Animals Arts Association Learning Axon BRAIN initiative Biological Brain Calcium Cell Communication Cells Communication Complex Cues Darkness Data Development Drosophila genus Educational process of instructing 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 Neurons Neurosciences North Carolina Odors Output Pathway interactions Physiological Physiology Population Positive Valence Predisposition Presynaptic Terminals Process Psyche structure Punishment Qualifying 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 body sense brain cell career cell type collaborative environment college connectome dopaminergic neuron experimental study extracellular fly gene therapy in vivo information gathering medical schools neuronal cell body next generation optogenetics presynaptic response sensory stimulus stimulus processing tool

项目摘要

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.

大脑使用许多细胞的组合生理学将传入的感觉信号转化为内部信号。表示。这个过程对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，并将它们与他们的情况相关联。虽然感官表征在体细胞水平的研究已经很充分，但缺乏在突触水平对这种现象的探索。这是一个重大因为单个轴突的单个突触前终扣可以被调节，这种差异性可能会影响学习和记忆。因此，这项建议的目的是扩大对突触前水平感觉信号产生的机械理解，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在突触前水平沿沿着单个轴突被调谐。基于此，本提案的假设代表性的突触前活动受到局部调制，可塑性的敏感性研究这一现象的一个合适模型是，果蝇嗅觉信息被传递到蘑菇体（MB）内的凯尼恩细胞（KC），和记忆中心。随着对单个KC轴突终扣的关注，本建议将探索突触表征和随后的学习诱导的可塑性，追求以下目标：（1）分析在突触和体细胞水平的代表性活动。(2)确定局部突触前神经元的起源调变(3)评估突触前表征活动与突触敏感性之间的联系可塑性这将通过使用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操作的潜力，轴轴调制的来源，最近确定的MB连接体。该项目的完成将进一步揭示了神经系统如何在学习过程中代表感官信息并调节这些信息。这将有助于大脑计划的长期目标，即理解感官信息是如何产生到更高级的过程，比如学习和感觉运动整合。这是通过使用“合成的战略”，跨越生物层次的水平（从突触到细胞到电路），以追求该倡议的近，长期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。的该提案还通过扩大申请人的技术能力，加强了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，通过支持严格的培训，由具有不同专业知识的合格顾问团队领导的协作环境。申办方的实验室位于北卡罗来纳州大学医学院和艺术学院的交界处它与北卡罗来纳州的许多果蝇和神经科学团体有着良好的联系。三角研究，为申请人提供丰富的资源，为独立的职业生涯做准备。