Dissection of genetic and epigentic factors controlling adult born neurons migration

在最复杂的器官——哺乳动物的大脑的发育过程中，从胚胎阶段到一个完全发育的有机体，最初的、粗糙的神经元连接转变为精确有序的回路，调节个体优化的感知和行为。在这一过程中，新神经元的产生、它们沿复杂路线的迁移以及它们与神经回路的整合是关键事件。细胞分化/存活、轴突和树突生长、突触形成/消除等过程有助于大脑中不同神经网络的形成和成熟。大脑的构造从胚胎时期开始，在出生后继续进行，并受到遗传和表观遗传因素的控制。破译控制大脑发育的机制以及这种组装的损害如何影响生理学是现代神经科学的关键问题。控制新神经元在离散位置产生的机制，它们在大脑中不同区域的迁移以及它们在成人大脑神经网络中的整合仍然不清楚，这是拟议研究项目的重点。我们建议从基因水平到行为水平研究控制成体神经元迁移的机制。具体来说，我们想了解一些引导线索及其相关受体如何影响神经突和核的运动，以及感觉经验如何控制迁移过程。为了解决这些问题，我们的目标是使用嗅觉系统作为模型系统，因为嗅球是受成人神经发生的影响。我们建议结合药理学、遗传学、影像学和行为学方法来解决这个项目中描述的问题。

During the development of the most complex organ, the mammalian brain, from the embryonic stage to a fully developed organism, the initial, coarse neuronal connections transform into precisely ordered circuits that mediate individually optimized perception and behavior. Production of new neurons, their migration along complex routes and their integration into the circuits are critical events during this process. The processes such as cell differentiation/survival, axonal and dendritic growths, and synapses formation/elimination contribute to the formation and maturation of the different neural networks in the brain. The brain construction, starting during embryonic life, continues postnatally and is under the control of genetic and epigenetic factors. Deciphering the mechanisms controlling brain development and how impairment of this assembly may affect physiology are key questions in modern Neuroscience.The mechanisms controlling the production of new neurons in discrete location, their migration to different regions in the brain and their integration in neural networks of the adult brain is still unclear and is the focus of the proposed research project. We propose to study the mechanisms controlling the migration of adult-born neurons starting from the level of genes up to the behavior level. Specifically, we would like to understand how some guiding cues and their associated receptors may influence neurites and nucleus motility and how the sensory experience control the migration process. To address these questions, we aim to use olfactory system as the model system since the olfactory bulb is subjected to adult neurogenesis. We propose to use a combination of pharmacological, genetic, imaging and behavioral methods, to address the questions described in this project.