Department of Anesthesiology and Critical Care

Description of Research Expertise

The overall goal my laboratory is to elucidate how substrates of the stress response are involved in medical or psychiatric disorders. Specific areas of interest include the serotonin neurotransmitter system and its projections to forebrain nuclei in the regulation of stress and in the development of mood disorders. Our work focuses on interactions between serotonin, GABA, glutamate, corticotropin-releasing factor-like peptide systems; the impact of long term stress on neuronal function; developmental regulation of the 5-HT limbic system; circuitry linking stress substrates to monoamine systems; stress substrates as targets for psychotherapeutic agents. We have determined, for example, that the basic cellular characteristics, morphology, cell number and excitatory and inhibitory synaptic input to 5-HT neurons within the different subfields of the dorsal and median raphe are different, and they are selectively modulated in genetically engineered mice that have an anxious phenotype or in animal models that have been subjected to stress protocols. In addition, the circuitry of the CA1 subfield of the hippocampus has been selectively altered. Recent work has focused on the development of the dorsal and median raphe serotonin and GABA neurons. Interestingly the physiology of serotonin neurons demonstrate an immature phenotype in the first week after birth, developing mature characteristics within two weeks. This two week period is a critical period where environmental, genetic, pharmacological, physiological or behavioral perturbations alter the serotonin neurons physiology, leading to a predisposition to develop mood disorders. We are investigating how these changes in the raphe in the first few weeks of life then alter the physiology of their projection areas, such as the medial prefrontal cortex, hippocampus and amygdala. The techniques and approaches in the lab include whole cell electrophysiology, in vitro and in vivo single unit electrophysiology, immunohistochemistry, neuroanatomy, cellular morphology, western blot, behavior, and the use of genetically manipulated mouse models of mood disorders. My laboratory has extensive collaborations with a variety of researchers, including geneticists and molecular biologists at CHOP, University of Pennsylvania as well as other institutions such as Harvard, Case Western, Columbia University.