Abstract: Series 102, Lecture 4
The Harvey Lectures Series 102 (2006—2007)
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Lecture #4: Thursday, February 22, 2007 — Time and Location
Signaling Networks that Control Synapse Development and Cognitive Function
Michael E Greenberg, PhD
Professor of Neurology
Professor of Neurobiology
Children’s Hospital, Neurobiology Program
Harvard Medical School
Boston, Massachusetts
Experience plays a crucial role in the development of the nervous system by promoting the maturation, and elimination of synapses. We have shown that synaptic stimulation by promoting calcium influx into neurons regulates a complex gene program that controls aspects of synapse development. We have identified a signaling network that conveys the calcium signal from the site of entry to the nucleus where transcription is activated. Of the activity-regulated genes, brain derived neurotrophic factor (BDNF) is one of the best characterized. Studies of BDNF gene regulation indicate the presence of a repressor complex bound to the BDNF promoter prior to stimulation that becomes replaced by an activator complex in stimulated cells. Mutations in MeCP2 a component of the BDNF repressor complex lead to Rett Syndrome an X linked human disorder marked by severe cognitive and motor impairment. Mutations in additional components of the activity-dependent signaling network also lead to cognitive impairment in humans indicating a critical role for this gene program in controlling normal cognitive function.