Department of Psychiatry Faculty

Patrick Allen, Ph.D. Assistant Professor of Psychiatry Ribicoff Research Facilities 34 Park Street Tel: 203-974-7763 Fax: 203-974-7897 Email: patrick.allen@yale.edu

Education

Ph.D., 1992, University of London

Research Interest

Our goal is to understand the molecular mechanisms that underlie nerve cell communication in the central nervous system. Synaptic function is governed by reversible protein phosphorylation, and the enzymes involved are tightly regulated at the synapse. Our focus is on the signal transduction machinery at excitatory synapses, with emphasis on the post-synaptic element found in dendritic spines.

Protein phosphatase activity in spines is particularly important for the regulation of synaptic strength. We have described several of the regulatory mechanisms involved. Spinophilin recruits protein phosphatase 1 (PP1) to the dense actin filament network that exists in spines. This complex serves to promote the activity of the phosphatase toward AMPA receptors, thereby controlling synaptic strength. An additional level of phosphatase control is provided by inhibitor 1, a PP1 regulatory subunit that is activated following stimulation of the cAMP pathway. This pathway is required for various forms of synaptic plasticity in different brain regions.

We are building on these findings with the analysis of additional aspects of spine physiology. Recent results indicate that spinophilin plays a role in the regulation of monoamine-mediated signal transduction. Current studies are underway to test the implications for adrenergic and dopaminergic activity in prefrontal cortex.

Lab personel:
Derek Haspeslagh, research assistant
Haleh Razani, postdoctoral associate

Publications of Note

Allen, P. B., Hvalby, Ø., Jensen, V., Errington, M. L., Ramsay, M., Chaudhry, F. A., Bliss, T. V. P., Storm-Mathisen, J, Morris, R. G. M., Andersen, P. and Greengard, P. (2000). Protein phosphatase-1 regulation in the induction of long-term potentiation: heterogeneous molecular mechanisms. Journal of Neuroscience 20: 3537-3543.

Feng, J., Yan, Z., Ferreira, A., Tomizawa, K., Liauw, J. A., Zhuo, M., Allen, P. B., Ouimet, C. C. & Greengard, P. (2000). Regulation of the Formation and Function of Dendritic Spines by Spinophilin. Proceedings of the National Academy of Sciences, U.S.A. 97: 9287-92.

Allen PB, Greenfield AT, Svenningsson P, Haspeslagh DC, Greengard P. Phactrs 1-4: A family of protein phosphatase 1 and actin regulatory proteins. Proc Natl Acad Sci U S A. 2004 May 4;101(18):7187-92. Epub 2004 Apr 23.

Allen PB. Functional plasticity in the organization of signaling complexes in the striatum. Parkinsonism Relat Disord. 2004 Jul;10(5):287-92.

Wang Q, Zhao J, Brady AE, Feng J, Allen PB, Lefkowitz RJ, Greengard P, Limbird LE. Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors. Science. 2004 Jun 25;304(5679):1940-4.

Wang X, Zeng W, Soyombo AA, Tang W, Ross EM, Barnes AP, Milgram SL, Penninger JM, Allen PB, Greengard P, Muallem S. Spinophilin regulates Ca2+ signalling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors. Nat Cell Biol. 2005 Apr;7(4):405-11.

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