Research Interests:

A fundamental question in neuroscience is how the structure and function of the brain is modified by experience. One compelling model of experience-dependent plasticity is behavioral sensitization-a long-lasting increase in the locomotor stimulatory effects of drugs of abuse following repeated exposure. Behavioral sensitization is also a prominent model for the intensification of drug craving that occurs in human addicts. My laboratory seeks to identify the cellular and molecular mechanisms that underlie this form of plasticity, as well as the genetic factors that may predispose an individual to sensitization. We are currently studying two cellular correlates of drug-induced plasticity, long-term depression at glutamatergic synapses in the nucleus accumbens-a key site of action of drugs of abuse in the brain-and the increases in the length of dendrites and the density of dendritic spines that also occur in accumbens neurons. We are using several complementary approaches to determine the relationship that each of these correlates has with behavioral sensitization and with each other: behavioral studies to determine the consequences of drug exposure, the use of transgenic and knockout mice, analysis of dendritic morphology via several staining methods and whole-cell recordings in brain slices to investigate synaptic function. These studies will provide insight into the cellular and molecular mechanisms of an important form of experience-dependent plasticity that may hold some of the clues to drug addiction.

Selected Publications:

Groth RD, Weick JP, Bradley KC, Luoma JI, Aravamudan B, Klug JR, Thomas MJ, Mermelstein PG. D1 dopamine receptor activation of NFAT-mediated striatal gene expression. Eur J Neurosci. 2008 Jan;27(1):31-42.

Kourrich S, Rothwell PE, Klug JR, Thomas MJ. Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens. J Neurosci. 2007 Jul 25;27(30):7921-8.

Sun M, Thomas MJ, Herder R, Bofenkamp ML, Selleck SB, O'Connor MB. Presynaptic contributions of chordin to hippocampal plasticity and spatial learning. J Neurosci. 2007 Jul 18;27(29):7740-50.

Thomas MJ, Malenka RC. Synaptic plasticity in the mesolimbic dopamine system. Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):815-9. Review..

Thomas, M.J., Malenka, R.C. and Bonci, A. (2000). Modulation of Long-term depression by dopamine in the mesolimbic system. Journal of Neuroscience 20: 5581-5586.

Thomas, M.J., Beurrier, C., Bonci, A. and Malenka, R.C. (2001). Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nature Neuroscience, 5 November 2001, DOI:10.1038/nn757

Thomas, M.J., Watabe, A.M., Moody, T.D., Makhinson, M., and O'Dell, T.J. (1998). Postsynaptic complex spike bursting enables the induction of LTP by theta frequency synaptic stimulation. Journal of Neuroscience 18: 7118-7126

Current Graduate Students:

Judy Kim (Neuroscience, University of Minnesota).

Rachel Penrod (Neuroscience, University of Minnesota).

Claudio Perez-Leighton (Neuroscience, University of Minnesota).

Patrick Rothwell (Neuroscience, University of Minnesota).