Mechanism of Spontaneous Activity in Embryonic Mouse Hindbrain

在哺乳动物大脑结构发育过程中，以动作电位形式出现的自发电活动已被证明是正确的电路布线和这些结构的细胞发育所必需的。然而，在许多这些结构中，自发活性的产生机制尚未阐明；在那些机制已知的地方，自发的电活动是由一个相互兴奋的神经元网络引起的，这些神经元网络相互同步活动。最近，该实验室已经证明，在早期胚胎小鼠的后脑，一个包含许多自主和广泛调节神经网络的区域，以及面部运动控制，同步的自发活动是由一个离散的神经元群控制的，新分化的中线血清素能区。这项拨款建议检查中线中缝神经元介导这种广泛的同步活动的机制，使用细胞内Ca2+水平的联合成像和单个神经元的电记录；此外，它将探索通过在控制和药理学改变条件下培养后脑来操纵活动的发展后果。了解这些机制，以及它们在改变药物条件下的调节作用，对于理解一个重要的大脑结构是如何发育的至关重要。PI将她的研究成果融入到她的本科教学中。7名本科生参加了先前资助的奖项。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被列为实验室至少一份主要出版物的作者。Bosma博士还参与了K-12和社区大学水平的外展活动，并资助当地社区大学的一名教师攻读研究生学位。PI积极参与从幼儿园到社区大学的学生的外展活动，通过开发和实施几个实践练习。她最近还获得了霍华德·休斯基金，将这项服务扩展到当地一所特殊教育教室的K-5残疾学生。PI还资助了一名从社区大学生物学教学休假的博士生。这名学生是市中心一所大学的终身讲师，为休假归来的年长学生提供服务，这些学生计划回到她的校园，更好地提供现代科学教育。支持本建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.