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果蝇学习和记忆中心神经微回路分区的发育及DIP-Dpr介导机制
结题报告
批准号:
81971075
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
谢晓军
依托单位:
学科分类:
神经系统发育与代谢异常
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
谢晓军
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中文摘要
学习和记忆是大脑的重要认知功能。既往研究表明脑发育过程中的认知功能障碍相关疾病的发生率呈逐年上升趋势,但其神经生物学机制仍不甚明了。蘑菇体是昆虫直接参与学习和记忆的神经中枢,沿着内源Kenyon细胞的轴突形成多个分区,输出神经元(MBON)和多巴胺神经元(DAN)投射到特定分区形成丰富的微回路。这种神经微回路的模式与其执行的学习和记忆功能相对应,但目前对其发育、形成及其分子机制仍知之甚少。本项目拟通过荧光标记记录蘑菇体神经元的发育过程,利用遗传诱导细胞死亡的方法探明特定蘑菇体神经元对分区发育和维持的重要性;并在前期研究发现免疫球蛋白超家族蛋白(Dpr和DIP)有着特定分区表达模式和对蘑菇体形态发生起作用的基础上,探讨其在神经微回路分区发育和形成中的功能,及其对突触、嗅觉学习和记忆功能的影响。研究结果将有助于阐明学习和记忆神经微回路发育形成的细胞和分子机制,为防治学习和记忆障碍提供新的思路。
英文摘要
Learning and memory is a fundamental cognitive function of our brains. Previous epidemiology studies indicate that the prevalence of cognitive disorders formed during brain development keeps increasing in recent years. However, the underlying biological mechanisms remain elusive. Mushroom body (MB) is the major learning and memory center in insect brains. Inside the MB, multiple compartments are formed along the axons of MB intrinsic neuron ‘Kenyon cells’. Each compartment is innervated by dendrites and/or axons of a specific type of MB output neurons (MBON) and dopaminergic neurons (DAN). This type of compartmentalized microcircuit organization correlates with the diverse roles that MB neurons play in learning and memory. However, the developmental and molecular mechanisms underlying MB compartment formation remain largely unknown. Our study will first record the developmental processes of different types of MB neurons by labeling their axons and dendrites with fluorescent markers. Then a specific type of MB neurons will be genetically ablated in pupae or in adult flies, and the neural processes of other related MB neurons will be examined in order to determining the importance of each neuronal type in MB compartment formation and maintenance..Our preliminary data show that two groups of immunoglobin (Ig) superfamily proteins, Dprs and DIPs, have specific expression patterns in MB compartments, and loss-of-function of one Dpr affects MB morphogenesis. We will investigate their functions in MB neuron development, MB compartment formation, MB synapse formation and olfactory learning and memory. Our work will document the cellular and molecular mechanisms underlying the development of learning and memory microcircuits, and may provide novel directions for preventing and treating learning and memory disorders.
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神经轴突生长与再生的转录因子分子机制研究
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    58万元
  • 批准年份:
    2021
  • 负责人:
    谢晓军
  • 依托单位:
国内基金
海外基金