Cellular and molecular mechanisms that temporally and spatially restrict synaptic

描述（由申请人提供）：5-羟色胺是一种神经递质，可调节广泛的行为和生理过程，包括进食、运动、生殖、呼吸、睡眠和情感。5-羟色胺能神经元在其发育、形态可塑性和功能方面是独特的。它们在特定的目标区域精心制作复杂的轴突乔木。这一发展的重要性反映在许多精神和认知障碍中，这些障碍的根源在于多巴胺能回路的不适当发展。5-羟色胺神经递质还能够反馈到多巴胺能神经元上，以可塑性地重塑轴突乔木和突触前释放位点。调节多巴胺能轴突和突触的发育和可塑性的分子机制还不清楚，这是本提案的目的。 5-羟色胺能途径在整个进化过程中是保守的。我们最近开发了一个系统，使我们能够在体内，在真实的时间和单细胞分辨率的C.优雅我们计划使用这个系统来回答以下问题：1）什么是细胞和分子机制，在空间上限制轴突分支？2)控制突触组装的分子机制是什么？控制Sertotonergic突触可塑性的分子机制是什么？ 总之，这里提出的方法将使我们能够剖析调节多巴胺能突触发育和可塑性的分子机制。考虑到多巴胺能神经回路的保守性，我们希望这些研究中发现的机制能够告知多巴胺能神经回路在发育和疾病中如何受到生理调节。

DESCRIPTION (provided by applicant): Serotonin is a neurotransmitter that modulates a wide range of behaviors and physiological processes, including feeding, movement, reproduction, respiration, sleep and affect. Serotonergic neurons are unique in terms of their development, morphological plasticity and function. They elaborate complex axon arbors over specific target regions. The importance of this development is reflected in the numerous psychiatric and cognitive disorders that have their roots in the improper development of serotonergic circuits. The serotonin neurotransmitter is also able to feed back onto serotonergic neurons to plastically reshape the axon arbors and presynaptic release sites. The molecular mechanisms that regulate the development and plasticity of serotonergic axon arbors and synapses are not yet understood, and are the purpose of this proposal. Serotonergic pathways are well conserved throughout evolution. We recently developed a system that allows us to assay serotonergic neuron morphogenesis and synaptogenesis in vivo, in real time and with single cell resolution in C. elegans. We plan to use this system to answer the following questions: 1) What are the cellular and molecular mechanisms that spatially restrict serotonergic axon arborization? 2) What are the molecular mechanisms the control serotonergic synapse assembly? and 3) What are the molecular mechanisms that control sertotonergic synapse plasticity? In summary, the approaches proposed here will allow us to dissect the molecular mechanisms that regulate serotonergic synapse development and plasticity. Given the conserved nature of serotonergic circuits, we expect the mechanisms uncovered in these studies to inform how serotonergic circuits are physiologically regulated in development and disease.