Mechanism of Spontaneous Activity in Embryonic Mouse Hindbrain

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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.