Discovery of sensorimotor connectivity mechanisms in a continuous topographic map

在连续地形图中发现感觉运动连接机制

• 批准号: 10557152
• 负责人: Cecilia B Moens
• 金额: $ 22万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557152
• 关键词: Address; Afferent Neurons; Anatomy; Animals; Axon; Baroreflex; Body part; Brain; Calcium; Cells; Complex; Cranial Nerves; Data; Development; Fishes; Gagging; Genetic; Goals; Heart; Image; Individual; Interneurons; Label; Larynx; Mammals; Maps; Motor; Motor Neurons; Motor output; Nerve; Neuroanatomy; Neurons; Neurosciences Research; Optics; Organ; Outcome; Pharyngeal structure; Physiological; Positioning Attribute; Proprioceptor; Reflex action; Role; Sensory; Specific qualifier value; Specificity; Spinal Cord; Stereotyping; Stomach; Synapses; System; Techniques; Testing; Unconscious State; Vagus nerve structure; Vertebrates; Visceral; Visualization; Work; Zebrafish; developmental neurobiology; functional group; genetic manipulation; hindbrain; insight; monosynaptic reflex; nervous system development; neural; neuronal circuitry; neurophysiology; postsynaptic; response; sensory input; sensory stimulus; sensory system; tool

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.

总结 这个项目的长期目标是了解神经连接的发展机制， 我们大脑中感觉运动反射回路的功能。反射回路使个体感觉输入能够引起功能性的反应， 适当的刻板运动输出，表明感觉之间存在细尺度的连接特异性 和运动系统。然而，在大脑中，负责不同功能的神经元通常是连续的， 在地形图上对齐，功能不同的神经元在边界区域混合 功能组之间。人们对地形图上功能不同的邻居 在反射回路发育过程中， 到感官信息。我们已经在幼斑马鱼中建立了迷走神经作为一个有效的系统， 来解决这个长期存在的大脑回路发展之谜。迷走神经离开后脑， 分支广泛，以支配咽、喉、胃、心脏和其他内脏器官。这条神经携带 感觉和运动轴突，其中每一个都参与几个多突触反射回路之一，包括 咽反射和压力反射。我们的小组已经发现迷走运动神经元和感觉轴突是 共同组织在一个连续的地形图，是在斑马鱼幼虫后脑内检测。我们的预- 初步数据支持对迷走神经感觉系统局部感觉输入选择性地激活功能性AP， 迷走神经运动神经元的适当群体具有惊人的精细尺度连接特异性， 相邻的功能不同的神经元为了研究这种功能分离的机制， 定量，我们将研究迷走神经运动神经元的神经活动的贡献，以实现精细的连接 特异性（目的1），我们将确定迷走神经反射回路的结构基础，通过跨突触 标签（目标2）。这些目标的成功结果将提供神经生理学和神经解剖学 深入了解脊椎动物整个感觉运动反射回路水平上的细尺度连接特异性 个脑袋斑马鱼幼体已经成为研究发育神经生物学的首要系统， 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作用的问题。 神经系统发育的其他方面。