The Emergence During Development of Spontaneous Synchronized Activity and its Pacemakers in Mouse Cerebral Cortex

这个项目的总体目的是了解自发电信号是如何在发育中的大脑中产生的。通过这个实验室和其他实验室的工作，人们现在了解到，自发电活动发生在大脑发育的特定阶段，并调节着大脑发育的许多重要方面。为了实现这些功能，这个活动必须在正确的时间开始，这样它才能有效地与大脑发育的其他方面相互作用，它必须在正确的时间停止，这样大脑处理感觉和运动信息的能力才能按计划出现。我们去年的实验表明，新生老鼠大脑中的自发活动会自动关闭。本项目的实验验证了这样一种观点，即这种活动也会自己开启——也就是说，在正确的发育阶段，高水平的自发活动出现需要少量的电活动。最近的实验也表明，新生小鼠大脑中的自发活动是由一组特定的起搏器神经元驱动的，这些神经元启动活动，然后将其传播到整个大脑。该项目的第二项研究将描述这些起搏器神经细胞的独特生理特性，这些生理特性赋予了它们这种起搏能力。所有这些实验都将通过单细胞电记录和光学成像方法的结合来完成。PI创建并指导了华盛顿大学的本科神经生物学专业。该课程将课堂学习与研究紧密结合，95%的学生从事独立研究。该项目规模小，师生联系密切，为少数民族学生提供了良好的指导环境。近3年来，该项目在其实验室共资助7名本科生。积极招募代表性不足的少数民族成员。这类学生约占神经生物学本科专业学生的15%。

The overall purpose of this project is to understand how spontaneous electrical signaling is generated in the developing brain. Through work of this laboratory and others, it is now understood that spontaneous electrical activity occurs at specific stages of brain development and regulates many important aspects of brain development. For these functions to be carried out, this activity must start at the right time so that it can interact efficiently with other aspects of brain development, and it must stop at the right time so that the ability of the brain to process sensory and motor information can appear on schedule. Our experiments during the last year have shown that spontaneous activity in the newborn mouse brain turns itself off. Experiments in the present project test the idea that this activity also turns itself on--that is, that small amounts of electrical activity are required for high levels of spontaneous activity to appear at the right developmental stage. Recent experiments have also shown that spontaneous activity in the newborn mouse brain is driven by a specific set of pacemaker neurons that initiate activity and then spread it across the entire brain. The second study in this project will characterize the unique physiological properties of these pacemaker nerve cells that give them this pacemaking ability. All of these experiments will be done with a combination of single-cell electrical recording and optical imaging methods.The PI created and directs the Undergraduate Neurobiology Major at the University of Washington. This program has a close link between classroom studies and research, and 95% of its students engage in independent research. The small size and close student-faculty contact in the program provide an excellent mentoring environment for minority students. The PI has sponsored 7 undergraduates from this program in his laboratory in the past 3 years. Members of underrepresented minorities are actively recruited. Such students constitute about 15% of the undergraduate majors in Neurobiology.