Spontaneous Activity in Embryonic Mouse Hindbrain Motor Neurons

了解自发电活动在大脑发育中的机制和作用，是全面理解单个神经细胞之间如何建立联系的关键。这些连接是成人大脑正常运作所必需的。后脑包含几组运动神经元，它们控制着在言语、呼吸和面部表情中起关键作用的肌肉。博斯马博士的实验室已经开发出在小鼠早期胚胎中识别特定后脑运动神经元的方法，并首次记录了在自发活动首次出现的发育阶段，这些已识别的胞体的自发活动。表征这些细胞的起始、特性和发育功能的能力使其成为了解自发活动在建立中枢神经系统和外周肌肉系统功能连接中所起作用的理想准备。由于PI的实验室已经开发出独特的方法来研究这种准备过程中的自发活动，PI已经与美国和欧洲的实验室建立了合作关系，这些实验室希望在雏鸟和斑马鱼的后脑中研究这些问题。这样的合作实验将有助于推进对依赖活动的后脑发育的进化和遗传学的理解。由于PI教授神经生物学和发育神经生物学的本科课程，研究努力将很容易融入本科教育。除了实验室中的其他本科生，PI已经赞助了三名本科生参与这一项目，其中一名目前在实验室，他是一篇关于这项工作的已发表论文的第一作者。其中两名学生获得了华盛顿大学佛朗哥奖最佳本科生研究论文奖。国际和平协会还参与了K-12和社区大学一级的教育推广活动。大脑功能和发育的基本理念已被纳入1-4年级的动手课堂练习，国际学生联合会已获得资金，将这一扩展扩展到当地K-5特殊教育教室的残疾学生。PI赞助了一名研究生，这名研究生的工资包括在这项提案中，她从当地一所社区大学休假，在那里她教生物。

Understanding the mechanisms and roles of spontaneous electrical activity in brain development is key to overall understanding of how connections among individual nerve cells are created. These connections are required for the correct functioning of the adult brain. The hindbrain contains several populations of motor neurons that control muscles serving critical functions in speech, respiration, and facial expression. Dr. Bosma's laboratory has developed methods for identifying specific hindbrain motor neurons in the early mouse embryo, and is the first to record spontaneous activity from these identified soma during the developmental stages when spontaneous activity first appears. The ability to characterize the onset, properties, and developmental functions of these cells makes this an ideal preparation in which to understand the role that spontaneous activity plays in establishing functional connections in the central nervous system and in the peripheral musculature. Because the PI's laboratory has developed unique methods to study spontaneous activity in this preparation, the PI has already established collaborations with laboratories in the US and Europe that wish to study these questions in chick and zebrafish hindbrain. Such collaborative experiments will help advance the understanding of the evolution and genetics of activity-dependent hindbrain development. Because the PI teaches undergraduate courses in neurobiology and developmental neurobiology, the research efforts will be easily integrated into undergraduate education. In addition to other undergraduates in the lab, the PI has already sponsored three undergraduate researchers to work on this project, including one currently in the lab who is the first author on a published paper on this work. Two of these students won the University of Washington's Franco Award for best undergraduate research paper. The PI is also involved in educational outreach at the K-12 and community college level. Basic ideas of brain function and development have been incorporated into grades 1-4 hands-on classroom exercises, and the PI has obtained funds to extend that outreach to disabled students in a local K-5 special education classroom. The PI sponsors a graduate student, whose salary is included in this proposal, who is on leave from a local community college, where she teaches biology.