Presynaptic Regulation of Dendritic Structural Dynamics

描述（由申请人提供）：发育神经科学的中心目标是阐明神经回路的形成、细化和维持背后的细胞机制。研究这些机制的实验策略是树突状乔木中形态变化的延时成像;虽然成像研究已经表明突触前神经活动影响树突结构，影响突触后形态的突触前活动参数仍不清楚。例如，在非洲爪蟾蝌蚪的视顶盖中，视觉刺激增强顶盖细胞树突状生长;然而，尚不清楚视网膜神经节细胞活性升高或刺激诱导的视网膜神经节细胞之间的相关性是否是额外生长的原因。通过表征神经节细胞的自发活动及其对各种视觉刺激的反应，将有可能开发系统地操纵其放电率和相关性的视觉刺激。播放这些刺激的蝌蚪，同时监测个别顶盖细胞树突状乔木的结构动力学，将直接测试突触前活动水平的重要性和调节突触后形态的相关性。此外，通过关联一些视网膜神经节细胞的活性，而不是具有可比活性水平的其他视网膜神经节细胞的活性，可以确定顶盖细胞是否偏好启动和/或稳定与相关输入的接触。最后，成像顶盖细胞的树突状动脉的能力，穗已被遗传降低，将区分顶盖细胞动作电位是否需要突触前调节顶盖树突。对突触前活动与树突结构可塑性相关的特征以及神经回路的形成有更深入的了解，将揭示更多关于潜在细胞机制的信息。特别地，将测试尖峰时间依赖性突触可塑性和树突结构可塑性的兼容性。这些研究将帮助我们了解视网膜活动如何影响大脑深处视觉回路的布线。这些知识将使我们能够更好地预测一些影响视网膜活动的眼病是否也可能导致这些电路中以前未检测到的布线缺陷，并设计策略来预防，改善或补偿这些缺陷。

DESCRIPTION (provided by applicant): A central goal in developmental neuroscience is to elucidate the cellular mechanisms behind the formation, refinement, and maintenance of neural circuits, An experimental strategy for studying these mechanisms is time lapse imaging of morphological changes in dendritic arbors; while imaging studies have shown that presynaptic neural activity influences dendritic structure, the parameters of presynaptic activity that influence postsynaptic morphology remain unclear. For example, in the optic tectum of Xenopus tadpoles, visual stimulation enhances tectal cell dendritic growth; however, it is unknown whether elevated retinal ganglion cell activity or stimulus induced correlations amongst retinal ganglion cells are responsible for the additional growth. By characterizing ganglion cells' spontaneous activity and their responses to a variety of visual stimuli, it will be possible to develop visual stimuli that systematically manipulate their firing rates and correlations. Playing these stimuli to tadpoles while monitoring the structural dynamics of individual tectal cell dendritic arbors, will directly test the importance of presynaptic activity levels and correlations for regulating postsynaptic morphology. In addition, by correlating the activity of some retinal ganglion cells, but not others with comparable activity levels, it is possible to determine whether or not tectal cells prefer initiating and/or stabilizing contacts with correlated inputs. Finally, imaging the dendritic arbors of tectal cells whose ability to spike has been genetically reduced, will distinguish whether or not tectal cell action potentials are required for presynaptic regulation of tectal dendrites. Greater understanding of the features of presynaptic activity relevant to dendritic structural plasticity, and therefore neural circuit formation, will reveal much about the underlying cellular mechanisms. In particular, the compatibility of spike timing dependent synaptic plasticity and dendritic structural plasticity will be tested. These studies will help us understand how retinal activity impacts wiring in visual circuits deeper in the brain. This knowledge will allow us to better predict whether some eye diseases that impact retinal activity might also cause previously undetected wiring defects in these circuits and design strategies to prevent, ameliorate, or compensate for these defects.