Department of Psychiatry Faculty

Education

B.A., 1992, Skidmore College
Ph.D., 1998, Stanford University

Laboratory personnel:

Jonathan Hommel, Graduate Student
Richard Trinko, Graduate Student
Robert Sears, Graduate Student
Laura Oskwarek, Research Assistant

Research Interest

Our goal is to establish an understanding of the molecular and neuronal circuits that are responsible for controlling reward-related behavior. We are particularly interested in defining brain mechanisms that regulate eating and are important in the development of obesity. Moreover, we hypothesize that dysfunction of these appetitive circuits also contributes to pathological states, such as eating disorders, drug addiction, and depression.

As a first step toward understanding the molecular changes that give rise to excessive consumption or restriction, we seek to identify the molecules and neural circuitry that connect initial metabolic signals to behavioral output. While the hypothalamus is critical for receiving metabolic signals, how these initial signaling events result in altered behavior remains unknown. Current projects in the lab are aimed at defining the molecular circuits that integrate the hypothalamus and peripheral metabolic signals with brain reward centers.

In addition, the lab is active in developing genetic and molecular tools that facilitate our efforts to better understand the molecular and cellular basis of neural plasticity and animal behavior. For example, our laboratory has pioneered the use of viral-mediated RNAi to create gene knockdowns in the brain. We will continue to develop powerful new techniques to better connect genes, neural anatomy and animal behavior.

Laboratory personnel:

Jonathan Hommel, Graduate Student
Richard Trinko, Graduate Studentbr
Robert Sears, Graduate Student
Laura Oskwarek, Research Assistant

Publications of Note

Georgescu, D., Sears, R.S., Hommel, J.D, Barrot, M., Marsh, D.J., Bednarek, M.A., Bibb, J.A., Maratos-Flier E., Nestler, E.J., and R.J. DiLeone (2005) The hypothalamic neuropeptide MCH acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. Journal of Neuroscience - in press.

Holder J.L., Zhang, L., Kublaoui, B.M., DiLeone, R.J., Oz, O.K., Bair C.H., Lee, Y.H., and A.R. Zinn (2004) Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice. American Journal of Physiology- Endocrinology and Metabolism, 287(1): E105-13.

Hommel, J.D., Sears, R.M., Georgescu, D., Simmons, D.L., and R. J. DiLeone (2003) Local gene knockdown in the brain using viral-mediated RNA interference. Nature Medicine 9(12): 1539-1544.

Georgescu, D., Zachariou, V., Barrot, M., Mieda, M., Willie, J.T., Eisch, A.J., Yanagisawa, M., Nestler, E.J., and R.J. DiLeone (2003) Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. Journal of Neuroscience 23(8): 3106-3111.

DiLeone, R.J., Georgescu, D., and E.J. Nestler (2003). Lateral hypothalamic peptides and drug addiction. Life Sciences 73:759-768.

Zachariou, V., Georgescu, D., Sanchez, N., Rahman, Z., DiLeone, R., Berton, O., Neve, R.L., Sim-Selley, L.J., Selley, D.E., Gold, S.J., and E.J. Nestler (2003) Essential role for RGS9 in opiate action. Proceedings of the National Academy of Sciences 100 (23): 13656-61.

Rahman, Z., Schwarz, J., Gold, S.J., Zachariou, V., Wein M.N., Choi, K.H., Kovoor, A., Chen C.K., DiLeone, R.J., Schwarz, S.C., Selley D.E., Sim-Selley, L.J., Barrot, M., Luedtke, R.R., Self, D., Neve, R.L., Lester, H.A., Simon, M.I., and E.J. Nestler (2003) RGS9 modulates dopamine signaling in the basal ganglia. Neuron, 38(6): 941-952.

Chao, J.R., Ni, Y.G., Bolaños, C.A., Rahman, Z., DiLeone, R.J., and E.J. Nestler (2002) Characterization of the mouse adenylyl cyclase type VIII gene promoter: Regulation by cAMP and CREB. European Journal of Neuroscience 16(7): 1284-1294.

Barrot, M., Olivier, J.D.A., Perrotti, L.I., DiLeone, R.J., Berton, O., Eisch, A.J., Impey, S., Storm, D.R., Neve, R.L., Yin, J.C., Zachariou, V., and E.J. Nestler (2002) CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. Proceedings of the National Academy of Sciences 99(17): 11435-11440.

Nestler, E.J., Barrot, M., DiLeone, R.J., Eisch, A.J., Gold, S.J., and L.M. Monteggia (2002). Neurobiology of Depression. Neuron 34(1): 13-25.

DiLeone, R.J., Marcus, G.M., Johnson, M.J., and D.M. Kingsley. (2000) Efficient studies of long-distance Bmp5 gene regulation using Bacterial Artificial Chromosomes (BACs). Proceedings of the National Academy of Sciences 97(4): 1612-1617.

DiLeone, R.J., Russell, L.B., and D.M. Kingsley. (1998) An extensive 3' regulatory region controls expression of Bmp5 in specific anatomical structures of the mouse embryo. Genetics 148(1): 401-408.

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