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.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Rothwell PE, Thomas MJ, Gewirtz JC. Protracted manifestations of acute dependence after a single morphine exposure. Psychopharmacology (Berl). 2011 Aug 11.
Penrod RD, Kourrich S, Kearney E, Thomas MJ, Lanier LM. An embryonic culture system for the investigation of striatal medium spiny neuron dendritic spine development and plasticity. J Neurosci Methods. 2011 Aug 30;200(1):1-13. Epub 2011 Jun 13.
Rothwell PE, Kourrich S, Thomas MJ. Synaptic adaptations in the nucleus accumbens caused by experiences linked to relapse. Biol Psychiatry. 2011 Jun 1;69(11):1124-6. Epub 2011 Feb 16.
Rothwell PE, Kourrich S, Thomas MJ. Environmental novelty causes stress-like adaptations at nucleus accumbens synapses: implications for studying addiction-related plasticity. Neuropharmacology. 2011 Dec;61(7):1152-9. Epub 2011 Feb 16.
Rothwell PE, Gewirtz JC, Thomas MJ. Episodic withdrawal promotes psychomotor sensitization to morphine. Neuropsychopharmacology. 2010 Dec;35(13):2579-89. Epub 2010 Sep 1.
Kourrich S, Thomas MJ. Similar neurons, opposite adaptations: psychostimulant experience differentially alters firing properties in accumbens core versus shell. J Neurosci. 2009 Sep 30;29(39):12275-83.
Rothwell PE, Thomas MJ, Gewirtz JC. Distinct profiles of anxiety and dysphoria during spontaneous withdrawal from acute morphine exposure. Neuropsychopharmacology. 2009 Sep;34(10):2285-95. Epub 2009 Jun 3.
Thomas MJ, Kalivas PW, Shaham Y. Neuroplasticity in the mesolimbic dopamine system and cocaine addiction. Br J Pharmacol. 2008 May;154(2):327-42. Epub 2008 Mar 17. Review.
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.
Current Graduate Students:
Rachel Penrod (Neuroscience, University of Minnesota).
Former Graduate Students:
Patrick Rothwell (Ph.D. 2010, Neuroscience, University of Minnesota).