Lab web page: http://markthomaslab.com/
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.)
- Ingebretson A, Hearing MC, Huffington ED, Thomas MJ. Endogenous dopamine and endocannabinoid signaling mediate cocaine-induced reversal of AMPAR synaptic potentiation in the nucleus accumbens shell. Neuropharmacology. 2018;131:154-165
- Hearing M, Graziane N, Dong Y, Thomas MJ. Opioid and psychostimulant plasticity: Targeting overlap in nucleus accumbens glutamate signaling. Trends Pharmacol Sci. 2018 Jan 12. pii: S0165-6147(17)30242-0.
- Ingebretson AE, Hearing MC, Huffington ED, Thomas MJ. Endogenous dopamine and endocannabinoid signaling mediate cocaine-induced reversal of AMPAR synaptic potentiation in the nucleus accumbens shell. Neuropharmacology. 2017;131:154-165
- Tonn Eisinger KR, Larson EB, Boulware MI, Thomas MJ, Mermelstein PG. Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors. Steroids. 2017 Nov 28. pii: S0039-128X(17)30224-6.
- Hearing MC, Jedynak J, Ebner SR, Ingebretson A, Asp AJ, Fischer RA, Schmidt C, Larson EB, Thomas MJ. Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement. Proc Natl Acad Sci U S A. 2016;113:757-62.
- Jedynak J, Hearing M, Ingebretson A, Ebner SR, Kelly M, Fischer RA, Kourrich SJ, Thomas MJ. Cocaine and amphetamine induce overlapping but distinct patterns of AMPAR plasticity in nucleus accumbens medium spiny neurons. Neuropsychopharmacology. 2016;41:464-76.
- Wydeven N, Marron Fernandez de Velasco E, Du Y, Benneyworth MA, Hearing MC, Fischer RA, Thomas MJ, Weaver CD, Wickman K. Mechanisms underlying the activation of G-protein-gated inwardly rectifying K+ (GIRK) channels by the novel anxiolytic drug, ML297. Proc Natl Acad Sci U S A. 2014;111(29):10755-60.
- Smith LN, Jedynak JP, Fontenot MR, Hale CF, Dietz KC, Taniguchi M, Thomas FS, Zirlin BC, Birnbaum SG, Huber KM, Thomas MJ, Cowan CW. Fragile X mental retardation protein regulates synaptic and behavioral plasticity to repeated cocaine administration. Neuron. 2014;82:645-58.
- Rothwell PE, Thomas MJ, Gewirtz JC. Protracted manifestations of acute dependence after a single morphine exposure. Psychopharmacology (Berl). 2012;219(4):991-8.
- 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;200(1):1-13.
- Rothwell PE, Kourrich S, Thomas MJ. Synaptic adaptations in the nucleus accumbens caused by experiences linked to relapse. Biol Psychiatry. 2011;69(11):1124-6.
- Rothwell PE, Kourrich S, Thomas MJ. Environmental novelty causes stress-like adaptations at nucleus accumbens synapses: implications for studying addiction-related plasticity. Neuropharmacology. 2011;61(7):1152-9.
Current Graduate Students:
Natalie Steenrod (Neuroscience, University of Minnesota)
Brian Sweis (Neuroscience, University of Minnesota).
Former Graduate Students:
Anna Ingebretson (Ph.D. 2017, Neuroscience, University of Minnesota).
Rachel Penrod (Ph.D. 2012, Neuroscience, University of Minnesota).
Patrick Rothwell (Ph.D. 2010, Neuroscience, University of Minnesota).