Mechanism of Spontaneous Activity in Embryonic Mouse Hindbrain

在哺乳动物大脑结构的发育中，自发的电活动以动作电位的形式被证明是这些结构的正确电路连接和细胞发育所必需的。然而，在许多这样的结构中，自发活动的产生机制还没有被阐明；在那些机制已知的结构中，自发电活动是由相互兴奋的神经元网络引起的，这些神经元相互同步活动。最近，该实验室发现，在早期胚胎小鼠的后脑中，一个包含许多自主神经和广泛的调制神经元网络以及面部运动控制的区域，同步的自发活动由一个离散的神经元群体控制，即新分化的中线5-羟色胺能中缝。这项资助建议通过结合细胞内钙离子水平的成像和单个神经元的电记录来研究中缝中线神经元介导这种广泛的同步活动的机制；此外，它还将通过在控制和药物改变的条件下培养后脑来探索操纵活动的发育分支。了解这些机制，以及它们被改变的药物条件所调节，对于了解一个重要的大脑结构是如何发展至关重要的。PI将她的研究成果整合到她的本科教学中。七名本科生参加了之前资助的奖项。这七名本科生中有四名获得了大学最佳本科生论文奖。这些本科生中有五人至少在实验室的一份主要出版物上被列为作者。博斯马博士还参与了K-12和社区大学一级的外展活动，并赞助当地社区学院的一名教师攻读研究生学位。国际学生协会通过制定和实施几个实践练习，积极参与从幼儿园到社区大学的外展活动。她最近还获得了霍华德·休斯的资金，将这一活动扩展到当地一所特殊教育教室里的K-5残疾学生。PI还赞助了一名正在社区大学生物教学中休假的博士生。这名学生是市中心一个校园的终身教员，为休过假的老学生和返校学生提供服务，她计划回到她的校园，更好地提供现代科学教育。支持本提议将使博斯马博士能够继续和扩大这些活动。

Spontaneous electrical activity, taking the form of action potentials, in developing mammalian brain structures has been shown to be required for the correct circuit wiring and cellular development of those structures. However, the mechanisms of generation of spontaneous activity have not been elucidated in many of these structures; in those where the mechanism is known, spontaneous electrical activity is caused by a network of mutually excitable neurons that synchronize each others activity. Recently, it has been shown by this laboratory that within the early embryonic mouse hindbrain, a region that contains many autonomic and widespread modulatory neuronal networks, as well as facial motor control, that synchronized spontaneous activity is controlled by a discrete population of neurons, the newly differentiating midline serotonergic raphe. This grant proposes to examine the mechanisms by which the midline raphe neurons mediate this widespread synchronized activity using combined imaging of intracellular Ca2+ levels and electrical recordings of individual neurons; in addition, it will explore the developmental ramifications of manipulation of the activity by culturing the hindbrain under control and pharmacologically altered conditions. Understanding these mechanisms, and their modulation by altered drug conditions, will be crucial to understanding how an important brain structure develops.The PI integrates her research results into her undergraduate teaching. Seven undergraduates participated in the previously funded award. Four of these seven undergraduate students won the University award for best undergraduate paper. Five of these undergraduates are listed as an author on at least one major publication from the lab. Dr. Bosma also participates in outreach at the K-12 and community college level and sponsors a teacher from a local community college to pursue a graduate degree The PI is actively involved in outreach for students from kindergarten through community college by developing and implementing several hands-on exercises. She has also recently obtained Howard Hughes funds to extend this outreach to K-5 students with disabilities in a local special education classroom. The PI also sponsors a PhD student who is on leave from community college biology teaching. This student is a tenured instructor at an inner city campus serving older and returning students who has taken a sabbatical, and who plans to return to her campus, better equipped to offer modern science education. Support of the present proposal will allow Dr. Bosma to continue and expand these activities.