Mark Thomas, Ph.D.
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.)
- Neuropsychopharmacology. 2023 Oct 16. doi: 10.1038/s41386-023-01752-8. Physiological acetic acid concentrations from ethanol metabolism stimulate accumbens shell medium spiny neurons via NMDAR activation in a sex-dependent manner.
- Chapp AD, Mermelstein PG, Thomas MJ. The ethanol metabolite acetic acid activates mouse nucleus accumbens shell medium spiny neurons. J Neurophysiol. 2021 Feb 1;125(2):620-627.
- Eisinger KRT, Chapp AD, Swanson SP, Tam D, Lopresti NM, Larson EB, Thomas MJ, Lanier LM, Mermelstein PG. Caveolin-1 regulates medium spiny neuron structural and functional plasticity. Psychopharmacology (Berl). 2020 Sep;237(9):2673-2684.
- Corkrum M, Covelo A, Lines J, Bellocchio L, Pisansky M, Loke K, Quintana R, Rothwell PE, Lujan R, Marsicano G, Martin ED. Thomas MJ, Kofuji P, Araque A. Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity. Neuron 2020;105(6):1036-1047.
- Corkrum M, Rothwell PE, Thomas MJ, Kofuji P, Araque A. Opioid-mediated astrocyte-neuron signaling in the nucleus accumbens. Cells. 2019 Jun 14;8(6):586.
- Benneyworth MA, Hearing MC, Asp AJ, Madayag A, Ingebretson AE, Schmidt CE, Silvis KA, Larson EB, Ebner SR, Thomas MJ. Synaptic depotentiation and mGluR5 activity in the nucleus accumbens drive cocaine-primed reinstatement of place preference. J Neurosci. 2019;39(24):4785-4796.
- Sweis BM, Thomas MJ, Redish AD. Beyond simple test of value: measuring addiction as a heterogeneous disease of computation-specific valuation processes. Learn. Mem. 2018;25:510-512.
- Sweis BM, Abram SV, Schmidt BJ, Seeland KD, MacDonald, AW III, Thomas MJ, Redish AD. Sensitivity to "sunk costs" in mice, rats, and humans. Science 2018;361:178-181.
- Sweis BM, Redish AD, Thomas MJ. Prolonged abstinence from cocaine or morphine disrupts separable valuations during decision conflict. Nat Commun. 2018 Jun 28;9(1):2521.
- Sweis BM, Thomas MJ, Redish AD. Mice learn to regret. PLoS Biol. 2018;16(6):e2005853.
- Sweis BM, Larson EB, Redish AD, Thomas MJ. Altering gain of the infralimbic-to-accumbens shell circuit alters economically dissociable decision-making algorithms. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6347-E6355.
- Ebner SR, Larson EB, Hearing MC, Ingebretson AE, Thomas MJ. Extinction and reinstatement of cocaine-seeking in self-administering mice is associated with Bidirectional AMPAR-mediated plasticity in the nucleus accumbens shell. Neuroscience. 2018 Jun 7;384:340-349.
- Hearing M, Graziane N, Dong Y, Thomas MJ. Opioid and Psychostimulant Plasticity: Targeting Overlap in Nucleus Accumbens Glutamate Signaling. Trends Pharmacol Sci. 2018 Mar;39(3):276-294.
- 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. 2018 Mar 15;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. 2018 May;133:53-59.
- 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.
Current Graduate Students:
Megan Brickner (Neuroscience, University of Minnesota).
Nolan Trevino (Neuroscience, University of Minnesota).
Former Graduate Students:
Brian Sweis (Ph.D. 2017, Neuroscience, University of Minnesota).
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).