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

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细胞 电路处理信息和执行计算，当失控时，很可能形成许多 神经和精神疾病。自主遗传程序和自发活动都被认为是 对突触的形成做出贡献。然而，自发活动的确切作用和机制 其产生的原因还没有被很好地理解。最近的研究证实，自发活动 伴随着果蝇视觉系统中突触的发育。此前人们认为苍蝇的大脑 仅通过预先编程的遗传协议来发育突触，这一观察是第一个证据 提示自发活动也可能有助于该系统的突触发生。初步研究表明 描述了这种活动的自然历史，它的传播机制，以及它在 单个细胞类型。值得注意的是，在成人中作为突触伙伴的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。广博的 苍蝇视觉系统中的遗传工具箱和绘制的连接组允许分子和细胞解剖 自发活动与突触形成的关系。拟议的研究计划将使用两个- 在果蝇中的光子钙成像和遗传优势，以阐明自发活动在 突触发生。进一步的研究将确定潜在的分子和细胞机制的产生和 自发活动的传播。这些结果将表明自发活动如何影响突触 并将为这一活动的机制提供重要的见解。 神经回路的组装。

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.