Karen M. Smith
1996 B.S., Cytogenetics, University of Connecticut, School of Allied Health, Storrs, CT
2003 Ph.D., Genetics, Tufts University, Sackler School of Graduate Biomedical Sciences, Boston, MA
2003-2005 Training Program in Childhood Neuropsychiatric Disorders. Yale University, Child Study Center, New Haven, CT
My primary interests are in the function of genes in orchestrating brain development in mammals, and the role that these developmental events play in neuropsychiatric disorders. My research focuses on genes that are important for the prenatal and postnatal development of the cerebral cortex in order to get a better understanding of the neurobiology of neuropsychiatric disorders. I use transgenic mouse models to study gene function in brain development, and in particular, the development of GABAergic inhibitory neurons. Mice lacking the fibroblast growth factor 1 gene (Fgfr1) in the brain develop profound hyperactivity that is characterized by an inability to stop motions once they have begun. This hyperactivity is correlated to the loss of a particular subset of neurons in the cortex of the brain called parvalbumin expressing (PV+) inhibitory interneurons. Similar decreases in PV+ interneurons have been observed in post mortem studies of individuals with schizophrenia or bipolar depression, and several animal models of autism have a decrease in inhibitory neurons. PV+ interneurons are thought to be important for coordinating brain rhythms so that excitatory neurons can fire in synchrony. This property contributes to the importance of studying the role of these neurons in cognition and behavioral control. We hypothesize that a relative imbalance of excitatory and inhibitory neurons in the cortex may contribute to disease. Therefore, understanding the factors that are involved in the development of PV+ interneurons may lead to novel treatment strategies for neuropsychiatric disorders. To this end, we are also interested in astrocytes, non-neuronal cells of the brain that express Fgfr1, and how they support the development of inhibitory interneurons. We employ a variety of approaches including microscopy, stereology (microscope-aided, unbiased cell counting approach), in vitro cell culture of neurons and astrocytes, targeted gene inactivation, behavioral experiments, and Translating Ribosome Affinity Purification (TRAP) to isolate mRNA and perform gene expression studies.