Determining the function and mechanism of spontaneous network activity during synaptogenesis in the Drosophila visual system

确定果蝇视觉系统突触发生过程中自发网络活动的功能和机制

• 批准号: 10362739
• 负责人: Bryce T Bajar
• 金额: $ 3.83万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-03-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362739
• 关键词: Adult; Affect; Attenuated; Axon; Biological Assay; Biological Models; Brain; Calcium; Cell physiology; Cells; Data; Development; Disease; Dissection; Dopamine; Drosophila genus; Drosophila melanogaster; Electron Microscopy; Etiology; Fire - disasters; Future; Gene Expression; Generations; Genes; Genetic; Human; Immunohistochemistry; Individual; Knock-out; Maps; Mediating; Mental disorders; Methods; Molecular; Molecular Genetics; Morphology; Natural History; Neurons; Neurophysiology - biologic function; Octopamine; Pathway interactions; Pattern; Periodicity; Phenotype; Photic Stimulation; Physiological; Process; Protocols documentation; Pupa; Research; Role; Schizophrenia; Serotonin; Stereotyping; Stimulus; Structure; Synapses; System; Time; Vertebrates; Visual system structure; Work; attenuation; autism spectrum disorder; base; cell type; connectome; course development; experimental study; fly; genetic analysis; genetic approach; imaging approach; imaging genetics; in vivo calcium imaging; insight; nervous system disorder; neural circuit; neurodevelopment; neuron development; neuronal circuitry; neuroregulation; neurotransmitter release; nodal myocyte; programs; relating to nervous system; synaptogenesis; two-photon; visual processing

ABSTRACT The human brain forms about 100 trillion synapses during development. These synapses determine how neural circuits process information and perform computations, and when dysregulated, likely form the basis of many neurological and psychiatric diseases. Both autonomous genetic programs and spontaneous activity are thought to contribute to synaptogenesis. However, the precise role of spontaneous activity and the mechanisms underlying its generation are not well understood. Recent work has established that spontaneous activity accompanies the development of synapses in the Drosophila visual system. The fly brain was previously thought to develop synapses solely via preprogrammed genetic protocols, and this observation is the first evidence to suggest that spontaneous activity may also contribute to synaptogenesis in this system. Preliminary studies have characterized the natural history of this activity, its mechanisms of propagation, and its patterns at the level of individual cell types. Remarkably, cells that are synaptic partners in the adult show correlated activity patterns. These data suggest that spontaneous activity is a fundamental phenomenon of circuit assembly. The extensive genetic toolbox and mapped connectome in the fly visual system allow for molecular and cellular dissection of the relationship between spontaneous activity and synapse formation. The proposed research plan will use two- photon calcium imaging and genetic advantages in Drosophila to elucidate the role of spontaneous activity in synaptogenesis. Further studies will identify molecular and cellular mechanisms underlying the generation and propagation of spontaneous activity. These results will indicate how spontaneous activity influences synapse formation in the developing brain and will provide important insights into the mechanisms of this activity in the assembly of neural circuits.

摘要 人类大脑在发育过程中形成了大约100万亿个突触。这些突触决定了神经元 电路处理信息并执行计算，当失调时，可能会形成许多 神经和精神疾病。自主遗传程序和自发活动都被认为是 对突触形成有贡献。然而，自发活动的确切作用和机制 其产生的根本原因还不清楚。最近的研究表明， 伴随着果蝇视觉系统突触的发育。苍蝇的大脑以前被认为 仅仅通过预先编程的遗传协议来开发突触，这一观察是第一个证据， 表明自发活动也可能有助于该系统中突触发生。初步研究已经 描述了这一活动的自然历史，其传播机制，以及其水平上的模式， 单个细胞类型。值得注意的是，成年人的突触伴侣细胞显示出相关的活动模式。 这些数据表明，自发活动是电路组装的基本现象。的广泛 果蝇视觉系统中的遗传工具箱和映射的连接体允许对果蝇进行分子和细胞解剖， 自发活动和突触形成之间的关系。该研究计划将使用两个- 光子钙成像和遗传优势，在果蝇阐明的作用，自发活动， 突触发生进一步的研究将确定产生的分子和细胞机制， 自发活动的传播。这些结果将表明自发活动如何影响突触 形成在发育中的大脑，并将提供重要的见解，这种活动的机制，在 神经回路的组装