Steven A. Thomas, MD< PhD

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				Steven A. Thomas, M.D., Ph.D. Associate Professor of Pharmacology Dept of Pharmacology School of Medicine 101/103 John Morgan Bldg/6084 (215) 573-4950 Lab: (215) 573-4951 Fax: (215) 573-2236 email: thomas@pharm.med.upenn.edu Click here for selected publications since Dr. Thomas' arrival at Penn RESEARCH INTEREST The roles of neurotransmission in development, neurophysiology and behavior. RESEARCH TECHNIQUES Mouse molecular genetics, in vitro and in vivo electrophysiology, gene expression analysis, pharmacology and behavioral studies. RESEARCH SUMMARY Broadly, the lab studies the development and physiology of the mammalian brain. One goal is to define the systems that contribute to specific behaviors, and to understand the mechanisms that underlie these behaviors. Such knowledge will ultimately permit the prevention and treatment of mental illness. Recent advances in transgenic technology allow the analysis of specific genetic alterations in the context of the whole organism. The ability to add, delete or modify genes is particularly useful in the analysis of complex organ systems such as the brain, where half of all genes are thought to be uniquely expressed. The lab focuses on the adrenergic nervous system in which norepinephrine (NE) and epinephrine are the classic neurotransmitters. By genetically eliminating the biosynthetic enzyme for NE, dopamine b -hydroxylase (DBH), mutant mice ( Dbh -/- ) that completely lack NE and epinephrine have been created. These mice are conditional mutants in that NE can be restored to the adrenergic terminals by supplying a synthetic amino acid precursor of NE, L-DOPS. The lab is pursuing several fundamental observations that resulted from the creation of these mutant mice. These include the critical role of NE in synaptic plasticity, learning and memory, sleep/wake regulation, anxiety, aggression, maternal behavior and the mechanisms of antidepressant drug action. We are also pursuing several novel genetic approaches for producing complementary models to the Dbh -/- mice toward a more complete understanding of CNS adrenergic function. KEY WORDS: Mouse molecular genetics, neural development, neurophysiology, norepinephrine, adrenergic nervous system, maternal behavior, learning and memory.