Stanley J. Watson, M.D., Ph.D.
Co-Director and Research Professor, MBNI
Theophile Raphael Professor of Neurosciences in Psychiatry

2022 MBNI Building
205 Zina Pitcher Place
Ann Arbor , MI 48109-0720

watsons@umich.edu

(734) 763-3725

Current Research Interests:

Emotional regulation of complex behaviors such as reinforcement, feeding, and stress are central to proper functioning of both animals and humans. This laboratory focuses on CNS circuits and cellular systems that participate and regulate these states and related pathological conditions. Using a variety of molecular, anatomical, behavioral and pharmacological approaches, it is possible to focus on key circuits and molecules of interests. These projects cover a wide range of topics:

1. Depression, bipolar disease and schizophrenia are all studied in postmortem human brain using microarrays across several regions of CNS. Families of genes have been found to be disregulated in these three major illnesses and are being further evaluated in animal studies. Most recently we and other members of the Pritzker Neuropsychiatric Disease Research Consortium have shown significant changes in Fibroblast Growth Factor, Mitochondria and immune gene families in major depression, bipolar disease, and schizophrenia respectively. In the near future broad-based genetic studies will be initiated in large sized patient sets.

Relationship of neurons regulating either motor function (green), or adrenal gland
function (red), or both (yellow and orange; indicated with arrows) to
serotonergic neurons (blue) in the rat brainstem.

2. Stress and substance abuse responsive systems have been mapped in rodent CNS using in situ hybridization of mRNA and intronic RNA for a large number of candidate molecules. By combining in situ regulatory studies with track tracing and other anatomical tools we have been able to describe how the brain responds to stress. Mixing these basic strategies with genetically altered mice has provided rich perspectives on the roles of the glucocorticoid receptor in mice. Similar analyses in high vs. low responder rats has been very powerful in revealing propensity to use drugs of abuse, for understanding some aspects of maternal behavior and for risk taking behavior. The regulation of important neural circuits is clearly altered in such animals.

3. Feeding systems in hypothalamus have been well studied for several neuropeptide systems, and their interconnections. Behavioral, gene knockouts, anatomical, and pharmacological approaches are often used. We have shown that major feeding control systems in hypothalamus are anatomically wired in a parallel fashion. These circuits are heavily dependent on melanocortin receptors 3 and 4 and have a substantial impact on Corticotrophin Releasing Hormone systems in the paraventricular nucleus.

Colocalization of MC4R mRNA and CRH in the PVN.  High magnification of microscopic images showing double-labeled cells.  Black arrows indicate cells double-labeled for
MC4R mRNA and CRH mRNA.  White arrows indicate cells labeled for MC4R mRNA only.

Selected Publications:

Lu, X.Y., Barsh, G.S., Akil, H., Watson, S.J.: Interaction between a -melanocyte-stimulating hormone and corticotropin-releasing hormone in the regulation of feeding and hypothalamo-pituitary-adrenal responses. J. Neurosci., 23(21):7863-7872, 2003.

Itoi, K., Jiang, Y.Q., Iwaski, Y., Watson, S.J.: Regulatory mechanisms of corticotropin-releasing hormone and vasopressin gene expression in the hypothalamus. J. Neuroendocrinology., 16:348-355, 2004.

Evans, S.J., Choudary, P.V., Neal, C.R., Li, J.Z., Vawter, M.P., Tomita, H., Lopez, J.F., Thompson, R.C., Meng, F., Stead, J.D., Walsh, D.M., Meyers, R.M., Bunney, W.E., Watson, S.J., Jones, E.G., Akil, H.: Dysregulation of the fibroblast growth factor system in major depression. Proc. Natl.Acad. Sci. U. S. A., 101(43):15506-15511, 2004.