Discovery of sensorimotor connectivity mechanisms in a continuous topographic map

摘要 该项目的长期目标是了解神经连接的发育机制。 我们大脑中感觉运动反射回路的稳定性。反射回路使个体的感觉输入能够产生功能-- 适当的刻板印象的运动输出，表明感觉之间有细微的联系特异性 和马达系统。然而，在大脑中，负责不同功能的神经元往往是连续的 在地形图上对齐，不同功能的神经元在边界区域混合在一起 在功能组别之间。人们很难理解地形图上不同功能的邻居是如何 在反射回路发育期间有所区别，因此它们总是能产生适当的反应 到感官信息。我们已经在斑马鱼幼体中建立了迷走神经作为一个有效的系统，在这个系统中 来解开大脑回路发育中这个长期存在的谜团。迷走神经离开后脑， 分支广泛，支配咽、喉、胃、心脏等脏器。这根神经承载着 感觉轴突和运动轴突，每个轴突都参与几个多突触反射回路之一，包括 咽部反射和压力反射。我们的团队发现迷走神经运动神经元和感觉轴突 共同组织在一张可在斑马鱼幼体后脑中检测到的连续地形图中。我们的前- 临床数据支持迷走神经感觉系统局部感觉输入选择性地激活功能性AP- 专属迷走运动神经元的组具有惊人的细微连接专一性，区分 相邻的功能不同的神经元。为了研究这种功能性隔膜的作用机制。 定量，我们将研究迷走神经运动神经元的神经活动对精细联系的贡献 特异性(目标1)，我们将确定通过跨突触精化迷走神经反射回路的结构基础 贴标签(目标2)。这些目标的成功结果将为神经生理学和神经解剖学提供 在脊椎动物整个感觉运动反射回路水平上对细微连接专一性的洞察 大脑。斑马鱼幼体已经成为研究发育神经生物学的首选系统，而且 我们在迷走神经系统中开发的工具将普遍适用于有关神经活动的作用的问题 在神经系统发育的其他方面。

SUMMARY The long-term goal of this project is to understand the developmental mechanisms underlying neural connectiv- ity within sensorimotor reflex circuits in our brain. Reflex circuits enable individual sensory inputs to elicit func- tionally appropriate stereotyped motor outputs, suggesting fine-scale connection specificity between the sensory and motor systems. However, in the brain, neurons responsible for different functions are often continuously aligned on topographic maps, with functionally different neurons being intermingled at the boundary regions between functional groups. It is poorly understood how functionally different neighbors on a topographic map are distinguished during reflex circuit development so that they can invariably generate appropriate responses to sensory information. We have established the vagus nerve in larval zebrafish as an efficient system in which to address this long-standing mystery in brain circuit development. The vagus nerve exits the hindbrain and branches widely to innervate the pharynx, larynx, stomach, heart and other visceral organs. This nerve carries both sensory and motor axons, each of which participates in one of several polysynaptic reflex circuits including the pharyngeal reflex and baroreflex. Our group has discovered that vagus motor neurons and sensory axons are co-organized in a continuous topographic map that is detectable within the larval zebrafish hindbrain. Our pre- liminary data support that local sensory inputs to the vagus sensory system selectively activate functionally ap- propriate groups of vagal motor neurons with a strikingly fine-scale connection specificity that distinguishes adjacent functionally different neurons. In order to investigate the mechanism underlying this functional sepa- ration, we will investigate the contribution of neural activity in vagal motor neurons for fine-scale connection specificity (Aim 1), and we will determine the structural basis of vagal reflex circuit refinement via transsynaptic labeling (Aim 2). The successful outcome of these aims will provide neurophysiological and neuroanatomical insights into fine-scale connection specificity at the level of entire sensorimotor reflex circuits in the vertebrate brain. The larval zebrafish has emerged as a premiere system in which to study developmental neurobiology, and the tools we develop in the vagus system will be generally applicable to questions about the role of neural activity in other aspects of nervous system development.