Michael M. Scott

Education

  • BS, Memorial University of Newfoundland
  • MS, Queen's University
  • PhD, Case Western Reserve University

Primary Appointment

  • Assistant Professor, Pharmacology

Contact

Research Interest(s)

Investigation of the neuronal circuits and epigenetic modifications involved in the control of food and drug reward

Research Description

We have three main projects that are ongoing in the laboratory.

The first project involves an investigation into the necessity and sufficiency of prefrontal cortical projections to the nucleus accumberns in driving changes in impulsive behavior, attention, food seeking behavior, social interaction, and anxiety behaviors. Our work involves a collaboration between Dr. Mark Beenhakker of the Department of Pharmacology and Dr. Manoj Patel of the Department of Anesthesiology.

A second project focuses on the population genetics of binge feeding. We have begun to examine, using the Diversity Outcross mouse population, quantitative trait loci (QTLs), expression QTLs and epigenomic QTLs that may responsible for driving excessive food intake. This project involves an active collaboration between the Scott lab, Dr. Mazhar Adli of Biochemistry and Molecular Genetics and Charles Farber of the Department of Public Health Science.

Finally, a third project focuses on the study of nicotine vapor self administration in mice. Our novel method allows us to model the way in which e-cigarettes or other vapor sources deliver nicotine and flavorings to the animal. We are currently testing the reinforcing properties of nicotine at concentrations that are currently commercially available, in adult and adolescent mice. We are also testing how flavorings affect the drive to self-administer vapor. We anticipate that future studies will be focused on the characterization of the epigenetic effects of nicotine vapor exposure and the neuronal cell types driving nicotine vapor seeking behavior. Our work involves a collaboration between Dr. Imad Damaj of Virginia Commonwealth University and Dr. Nadine Kabbani, of George Mason University. This project is currently funded through the Virginia Foundation for Healthy Youth (VFHY) Large Grant Mechanism, titled: Investigation of nicotine vapor self-administration in mice.

Selected Publications

  • Gaykema R, Nguyen X, Boehret J, Lambeth P, Joy-Gaba J, Warthen D, Scott M. Characterization of excitatory and inhibitory neuron activation in the mouse medial prefrontal cortex following palatable food ingestion and food driven exploratory behavior. Frontiers in neuroanatomy. 2014;8 60. PMID: 25071465 | PMCID: PMC4076747
  • Williams K, Liu T, Kong X, Fukuda M, Deng Y, Berglund E, Deng Z, Gao Y, Liu T, Sohn J, Jia L, Fujikawa T, Kohno D, Scott M, Lee S, Lee C, Sun K, Chang Y, Scherer P, Elmquist J. Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis. Cell metabolism. 2014;20(3): 471-82. PMID: 25017942 | PMCID: PMC4186248
  • Berglund E, Vianna C, Donato J, Kim M, Chuang J, Lee C, Lauzon D, Lin P, Brule L, Scott M, Coppari R, Elmquist J. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. The Journal of clinical investigation. 2012;122(3): 1000-9. PMID: 22326958 | PMCID: PMC3287225
  • Scott M, Perello M, Chuang J, Sakata I, Gautron L, Lee C, Lauzon D, Elmquist J, Zigman J. Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose. PloS one. 2012;7(8): e44089. PMID: 22952883 | PMCID: PMC3432098
  • Donato J, Cravo R, Fraz√£o R, Gautron L, Scott M, Lachey J, Castro I, Margatho L, Lee S, Lee C, Richardson J, Friedman J, Chua S, Coppari R, Zigman J, Elmquist J, Elias C. Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. The Journal of clinical investigation. 2010;121(1): 355-68. PMID: 21183787 | PMCID: PMC3007164
  • Gautron L, Lazarus M, Scott M, Saper C, Elmquist J. Identifying the efferent projections of leptin-responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach. The Journal of comparative neurology. 2010;518(11): 2090-108. PMID: 20394060 | PMCID: PMC3198871
  • Williams K, Margatho L, Lee C, Choi M, Lee S, Scott M, Elias C, Elmquist J. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010;30(7): 2472-9. PMID: 20164331 | PMCID: PMC2836776
  • Scott M, Lachey J, Sternson S, Lee C, Elias C, Friedman J, Elmquist J. Leptin targets in the mouse brain. The Journal of comparative neurology. 2009;514(5): 518-32. PMID: 19350671 | PMCID: PMC2710238
  • Jensen P, Farago A, Awatramani R, Scott M, Deneris E, Dymecki S. Redefining the serotonergic system by genetic lineage. Nature neuroscience. 2008;11(4): 417-9. PMID: 18344997 | PMCID: PMC2897136
  • Lim C. S., Hoang E. T., Viar K. E., Stornetta R. L., Scott M. M., Zhu J. J.. Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model Genes Dev. 28(3): 273-89.
  • Perello M., Chuang J. C., Scott M. M., Lutter M.. Translational neuroscience approaches to hyperphagia J Neurosci. 30(35): 11549-54.
  • Perello M., Scott M. M., Sakata I., Lee C. E., Chuang J. C., Osborne-Lawrence S., Rovinsky S. A., Elmquist J. K., Zigman J. M.. Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain J Comp Neurol. 520(2): 281-94.
  • Rossi J., Balthasar N., Olson D., Scott M., Berglund E., Lee C. E., Choi M. J., Lauzon D., Lowell B. B., Elmquist J. K.. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis Cell Metab. 13(2): 195-204.
  • Scott M. M., Deneris E. S.. Making and breaking serotonin neurons and autism Int J Dev Neurosci. 23(2): 277-85.
  • Scott M. M., Krueger K. C., Deneris E. S.. A differentially autoregulated Pet-1 enhancer region is a critical target of the transcriptional cascade that governs serotonin neuron development J Neurosci. 25(10): 2628-36.
  • Scott M. M., Marcus J. N., Elmquist J. K.. Orexin neurons and the TASK of glucosensing Neuron. 50(5): 665-7.
  • Scott M. M., Marcus J. N., Pettersen A., Birnbaum S. G., Mochizuki T., Scammell T. E., Nestler E. J., Elmquist J. K., Lutter M.. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors Behav Brain Res. 222(2): 289-94.
  • Scott M. M., Williams K. W., Rossi J., Lee C. E., Elmquist J. K.. Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice J Clin Invest. 121(6): 2413-21.
  • Scott M. M., Wylie C. J., Lerch J. K., Murphy R., Lobur K., Herlitze S., Jiang W., Conlon R. A., Strowbridge B. W., Deneris E. S.. A genetic approach to access serotonin neurons for in vivo and in vitro studies Proc Natl Acad Sci U S A. 102(45): 16472-7.
  • Scott M. M., Xu Y., Elias C. F., Williams K. W.. Central regulation of food intake, body weight, energy expenditure, and glucose homeostasis Front Neurosci. 8 384.
  • Scott M., Tanguay J. J., Beninger R. J., Jhamandas K., Boegman R. J.. Neurosteroids and glutamate toxicity in fibroblasts expressing human NMDA receptors Neurotox Res. 4(3): 183-90.
  • Sisley S., Gutierrez-Aguilar R., Scott M., D'Alessio D. A., Sandoval D. A., Seeley R. J.. Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect J Clin Invest. 124(6): 2456-63.
  • Vianna C, Donata J, Rossi J, Scott M, Economides K, Gautron L, Pierpont S, Elias C, Elmquist J. Cannabinoid receptor 1 in the vagus nerve is dispensable for body weight homeostasis but required for normal gastrointestinal motility J. Neurosci. 32(30): 10331-7.
  • Warthen D. M., Lambeth P. S., Ottolini M., Shi Y., Barker B. S., Gaykema R. P., Newmyer B. A., Joy-Gaba J., Ohmura Y., Perez-Reyes E., Guler A. D., Patel M. K., Scott M. M.. Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake Front Behav Neurosci. 10 63.
  • Williams K. W., Scott M. M., Elmquist J. K.. From observation to experimentation: leptin action in the mediobasal hypothalamus Am J Clin Nutr. 89(3): 985S-990S.
  • Williams K. W., Scott M. M., Elmquist J. K.. Modulation of the central melanocortin system by leptin, insulin, and serotonin: Co-ordinated actions in a dispersed neuronal network Eur J Pharmacol. 660(1): 2-12.
  • Xu X., Scott M. M., Deneris E. S.. Shared long-range regulatory elements coordinate expression of a gene cluster encoding nicotinic receptor heteromeric subtypes Mol Cell Biol. 26(15): 5636-49.
  • Zechner J. F., Mirshahi U. L., Satapati S., Berglund E. D., Rossi J., Scott M. M., Still C. D., Gerhard G. S., Burgess S. C., Mirshahi T., Aguirre V.. Weight-independent effects of roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans Gastroenterology. 144(3): 580-590 e7.
  • Zhao Z. Q., Chiechio S., Sun Y. G., Zhang K. H., Zhao C. S., Scott M., Johnson R. L., Deneris E. S., Renner K. J., Gereau R. W. th, Chen Z. F.. Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs J Neurosci. 27(22): 6045-53.
  • Zhao Z. Q., Scott M., Chiechio S., Wang J. S., Renner K. J., Gereau R. W. th, Johnson R. L., Deneris E. S., Chen Z. F.. Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity J Neurosci. 26(49): 12781-8.