Mark Thomas, PhD
Professor, Department of Neuroscience
Professor, Department of Neuroscience
Preceptor, Graduate Program in Neuroscience
Medical Scientist Training Program (Combined MD/PhD Training Program)
Summary
Mark Thomas is a professor of neuroscience and director of the Medical Discovery Team on Addiction, a new research program funded by the state legislature to fuel cross-disciplinary collaborations and discover new treatment options. His research examines how addictive drugs alter the brain and how these changes can lead to compulsive drug use. His lab is now focusing on ways to disrupt addiction relapse.
Research
Research Summary/Interests
Neurobiology of drug-induced plasticity and addiction
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.
Publications
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. doi: 10.1152/jn.00659.2020.
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. doi: 10.1007/s00213-020-05564-2.
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 2020, 'Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity', Neuron. https://doi.org/10.1016/j.neuron.2019.12.026
Madayag, AC, Gomez, D, Anderson, EM, Ingebretson, A, Thomas, MJ & Hearing, MC 2019, 'Cell-type and region-specific nucleus accumbens AMPAR plasticity associated with morphine reward, reinstatement, and spontaneous withdrawal', Brain Structure and Function, vol. 224, no. 7, pp. 2311-2324. https://doi.org/10.1007/s00429-019-01903-y
Benneyworth, MA, Hearing, MC, Asp, AJ, Madayag, A, Ingebretson, AE, Schmidt, CE, Silvis, KA, Larson, EB, Ebner, SR & Thomas, MJ 2019, 'Synaptic depotentiation and mGluR5 activity in the nucleus accumbens drive cocaine-primed reinstatement of place preference', Journal of Neuroscience, vol. 39, no. 24, pp. 4785-4796. https://doi.org/10.1523/JNEUROSCI.3020-17.2019
Sweis, BM, Redish, D & Thomas, MJ 2018, 'Prolonged abstinence from cocaine or morphine disrupts separable valuations during decision conflict' Nature Communications, vol. 9, no. 1, 2521. https://doi.org/10.1038/s41467-018-04967-2
Sweis, BM, Thomas, MJ & Redish, D 2018, 'Beyond simple tests of value: Measuring addiction as a heterogeneous disease of computation-specific valuation processes' Learning and Memory, vol. 25, no. 9, pp. 501-512. https://doi.org/10.1101/lm.047795.118
Ebner, SR, Larson, EB, Hearing, MC, Ingebretson, AE & Thomas, MJ 2018, 'Extinction and Reinstatement of Cocaine-seeking in Self-administering Mice is Associated with Bidirectional AMPAR-mediated Plasticity in the Nucleus Accumbens Shell' Neuroscience, vol. 384, pp. 340-349. https://doi.org/10.1016/j.neuroscience.2018.05.043
Sweis, BM, Abram, SV, Schmidt, BJ, Seeland, KD, MacDonald, A, Thomas, MJ & Redish, D 2018, 'Sensitivity to “sunk costs” in mice, rats, and humans' Science, vol. 361, no. 6398, pp. 178-181. https://doi.org/10.1126/science.aar8644
Sweis, BM, Larson, EB, Redish, D & Thomas, MJ 2018, 'Altering gain of the infralimbic-to-accumbens shell circuit alters economically dissociable decision-making algorithms' Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 27, pp. E6347-E6355. https://doi.org/10.1073/pnas.1803084115
Sweis, BM, Thomas, MJ & Redish, D 2018, 'Mice learn to avoid regret' PLoS Biology, vol. 16, no. 6, e2005853. https://doi.org/10.1371/journal.pbio.2005853
Tonn Eisinger, KR, Larson, EB, Boulware, MI, Thomas, MJ & Mermelstein, PG 2018, 'Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors' Steroids, vol. 133, pp. 53-59. https://doi.org/10.1016/j.steroids.2017.11.013