Suzanne Paradis (Brandeis University)
MolBio Seminar Series
Dr. Paradis received her BA from Cornell University and her PhD in Genetics from Harvard Medical School. Her thesis research, performed in the laboratory of Dr. Gary Ruvkun, investigated the genetic program that regulates lifespan in the nematode C. elegans. During her postdoctoral fellowship in the lab of Dr. Michael Greenberg at Harvard Medical School, she pioneered the use of RNAi in cultured hippocampal neurons to identify new molecules required for synapse formation. Her own lab at Brandeis University focuses on how intact circuits form in the mammalian CNS by defining the genes that instruct neurons to modify their synaptic connections and dendritic morphology in response to changes in sensory experience.
Signaling Pathways that Instruct Rapid Changes in Neuronal Connectivity
The overall structure and function of circuits in the central nervous system is established by a variety of carefully orchestrated processes, including the formation of synapses and the morphogenesis of the dendritic arbor of individual neurons. Further, while it is well-established that sensory experience sculpts connections in the nervous system, it is not at all understood how this is accomplished at the molecular level. My lab focuses on identifying and defining the function of genes that regulate neuronal connectivity and structural plasticity both in the context of changes in sensory experience and nervous system development. We recently discovered that the activity-dependent expression of the GTPase Rem2 functions as a critical regulator of activity-dependent dendritic branching, as dialing Rem2 expression up or down in the context of increased sensory experience in an intact circuit decreases or increases dendritic branching accordingly. Overall, our studies of Rem2 reveal a previously unappreciated signaling paradigm whereby increased neuronal activity simultaneously initiates signal transduction networks that either promote or restrict dendritic arborization. In addition, our studies of synapse formation revealed that treatment of cultured neurons with the extracellular domain of the protein Sema4D causes a rapid increase (i.e. within 2 hours) in the density of functional GABAergic synapses. Using an organotypic hippocampal slice culture as an in vitro model of epileptiform activity, we demonstrated that acute Sema4D treatment rapidly and dramatically alters the hyperexcitability found in these slices in a manner consistent with a Sema4D-mediated increase in network inhibition. Our studies suggest the tantalizing possibility that Sema4D, as well as other molecules that instruct formation of GABAergic synapses, could be used as a disease-modifying treatment for epilepsy.
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