Project Summary

Rita J. Valentino, Ph.D. (Distinguished Investigator 2002) of Children's Hospital of Philadelphia, points out that recent studies have revealed a role for neuropeptides, specifically corticotropin-releasing factor (CRF) and Substance P (SP), in affective disorders.  This has sparked the development of novel therapeutic agents that target these peptides.  The efficacy of drugs that target the neuropeptides, as well as drugs that target serotonin (5-HT) suggest that loci in circuits where these neuromediators converge may be the focus of the pathophysiology.  Elucidating interactions between these neuromediators at these loci of convergence is critical to understanding the pathophysiology of affective disorders and providing a rationale for the development of therapeutic agents.  Dr. Valentino recently identified a point of convergence within the dorsal raphe nucleus (DR) where 5-HT, CRF and SP may interact.  The DR, a major source of 5-HT cell bodies that project to forebrain regions involved in cognition and emotion, can be divided into subnuclei that have distinct afferent and efferent connections.  She will use a novel approach of intracellular labeling following juxtacellular neuronal recording in vivo.  This powerful approach has been used to characterize cardiovascular responsive neurons in the medulla and she recently had success using this technique to intracellularly label Barrington's nucleus neurons following recording responses to visceral stimulation.  Dr. Valentino hopes to further develop the approach of in vivo intracellular labeling from biogenic amine neurons.  This is a powerful technique because it allows her to characterize the morphology, neurochemical identity, sensitivity to various stimuli and neural connectivity within a system, which cannot be done in vitro.  A long range plan is to use this approach to manipulate gene expression of selected neurons in this region and determine the impact of this on behavior.

Program Area: MOOD DISORDERS\Mood Disorders (General)

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