Edwin W Rubel, Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology- Head and Neck Surgery, Department of Physiology and Biophysics, University of Washington, Seattle

Since the classic experiments of Hamburger, Levi-Montalcini, and Hubel & Wiesel, a large variety of studies have shown that manipulations of peripheral input and sensory experience can have profound influences on the development of sensory encoding pathways of the central nervous system. We have used the brainstem auditory pathways of birds and mammals to investigate the early cellular events underlying deprivation- and deafferentation-induced changes in the structure and integrity of neurons and glial cells. Our work in this area uses a variety of methodologies on in vivo and in vitro preparations of the brainstem to address three issues related to activity-regulated development and maintenance of auditory brainstem neurons. What is the nature of the intercellular signals regulating structural integrity of postsynaptic neurons? What are some of the intracellular cascades of events underlying deprivation-induced changes in neuronal integrity? What biological mechanisms may underlie developmental differences in responses to peripheral manipulations (critical periods)? I will briefly summarize our approach to these problems and then discuss recent and ongoing experiments focused toward understanding the differential susceptibility of neonatal and adult sensory systems to neuronal death due to deprivation of afferent activity (a critical period) using normal and transgenic mice, and microarray technology.