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Indiana University Bloomington

George Rebec

Dr. George Rebec

Chancellor's Professor of Psychological and Brain Sciences

 

rebec [at] indiana.edu

office: PY 361 | (812)855-4832

lab: Preclinical Pharmacology Laboratory
   PY A422 | (812)855-5351

 

Mechanisms of action of drugs of abuse; neurochemical correlates of movement and motivation; real-time assessments of neurotransmitter function during behavior; genetic and neurotoxic models of neurodegenerative disease

Educational Background

  • 1971 - B.A., Villanova University
  • 1974 - M.A., University of Colorado at Boulder
  • 1975 - Ph.D., University of Colorado at Boulder

Areas of Study

  • Molecular and Systems Neuroscience
  • Behavioral Neuroscience

Research Topics

  • Transgenic models of neurodegenerative disease
  • Behavior-related neuronal processing in forebrain networks
  • Cortico-limbic circuits underlying drug addiction
  • Mechanisms of information exchange in cortico-striatal circuits

Research Summary:

Research in my laboratory focuses on the neural mechanisms underlying basic behavioral processes such as habit learning, motor control, and motivation. We are especially interested in cortical interactions with the basal ganglia and related limbic nuclei. Dysfunctional cortical-subcortical circuitry is central to the development of drug craving, plays a critical role in the signs and symptoms of several neurological diseases, and may contribute to motor deficits with aging. To assess how these brain systems operate and interact under freely behaving conditions, we combine electrophysiological approaches (single-unit recording and local field potentials) with recent analytical innovations (coherence assessment and causality detection). We also use electrochemical (slow- and fast-scan cyclic voltammetry) techniques along with genomic and proteomic analyses to measure neurotransmitter function at the neuronal level during behavior.

A primary area of interest is the change in neuronal information processing induced by cocaine and other psychomotor stimulants. We have a long-standing program aimed at investigating the role of dopamine and its interaction with glutamate in addiction and relapse. Another primary area of interest is the neural network dysfunction underlying Huntington’s disease, an autosomal dominant and fatal neurodegenerative condition. In both of these areas of interest, we are developing therapeutic targets centered on the clearance of glutamate from forebrain extracellular fluid.

Further information on our research programs are available at: www.indiana.edu/~basalgan/

Representative Publications

Murphy-Nakhnikian, A., Rebec, G.V. (2014), Grasse, L. M., Dwiel, L. O., Shimono, M., Beggs, J. M. Behavioral modulation of reciprocal corticostriatal influence during awake, spontaneous behavior in rats. PLoS ONE, in press.

Rebec, G.V. (2013) Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington’s disease. Antioxidants and Redox Signaling, 19:2115-2128.

Fischer, K. D., Houston, A.C.W., & Rebec, G.V. (2013). Role of the major glutamate transporter GLT1 in nucleus accumbens core vs. shell in cue-induced cocaine seeking behavior. Journal of Neuroscience, 33:9319-9327.

Estrada-Sanchez, A.M., Barton, S.J. & Rebec, G.V. (2013) Altered neuronal dynamics in the striatum on the behavior of huntingtin interacting protein 14 (HIP14) knockout mice. Brain Sciences, 3:1588-1596.

Estrada-Sanchez, A.M., Barton, S.J., Burroughs, C.L., Doyle, A.R., & Rebec, G.V. (2013) Dysregulated striatal neuronal processing and impaired motor behavior in mice lacking huntingtin interacting protein 14 (HIP14). PLoS ONE, 8(12): e84537. doi:10.1371.

Estrada-Sanchez, A.M. & Rebec, G.V. (2013). Role of cerebral cortex in the neuropathology of Huntington’s disease. Frontiers in Neural Circuits, 7:19. doi:10.3389.

Hong, S. L., Cossyleon, D., Hussain, W. A., Walker, L. J., Barton, S. J. & Rebec, G.V. (2012). Dysfunctional behavioral modulation of corticostriatal communication in the R6/2 mouse model of Huntington’s disease. PloS One, 7(10): E47026, 1-9.

Hong, S. L., & Rebec, G.V. (2012). Biological sources of inflexibility in brain and behavior with aging and neurodegenerative diseases. Frontiers in Systems Neuroscience, 6 (77):1-11.

Hong, S.L., Barton, S.J., & Rebec, G.V. (2012). Altered neural and behavioral dynamics in Huntington’s disease: An entropy conservation approach. PLoS ONE, 7 (1), e30879.

Murphy-Nakhnikian, J. M., Dorner, J. L., Fischer, B. I., Bower-Bir, N. D., & Rebec, G. V. (2012). Abnormal burst patterns of single neurons recorded in the substantia nigra reticulata of behaving 140 CAG Huntington’s disease mice. Neuroscience Letters, 512, 1-5.

Miller, B. R., Dorner, J. L., Bunner, K. D., Gaither, T. W., Klein, E. L., Barton, S. J., & Rebec, G.V. (2012). Upregulation of GLT1 reverses the deficit in cortically evoked striatal ascorbate efflux in the R6/2 mouse model of Huntington’s disease. Journal of Neurochemistry, 121, 629-638.

Fischer-Smith, K. D., Houston, A.C.W., & Rebec, G.V. (2012). Differential effects of cocaine access and withdrawal on GLT1 expression in rat nucleus accumbens core and shell, Neuroscience, 210: 333-339.

Hong, S.L., Barton, S.J., & Rebec, G.V. (2012). Neural correlates of unpredictability in behavioral patterns of wild-type and R6/2 mice. Commun Integr Biol, 5(3):1-3.

Estrada Sánchez, A.M. & Rebec, G.V. (2012). Corticostriatal dysfunction and glutamate transporter 1 (GLT1) in Huntington’s disease: interactions between neurons and astrocytes. Basal Ganglia, 2, 57-66.

Wilber, A. A., Walker, A., Southwood, C. Rebec, G.V., and Wellman, C. (2011). Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction. Neuroscience, 174:115-131.

Xue, Y. Q., Steketee, J., Rebec, G., & Sun, W. L. (2011). Activation of D2-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug seeking-behavior. European Journal of Neuroscience, 33(7), 1291-1298.

Sari, Y., Sakai, M., Weedman J. M., Rebec G.V., & Bell R. L. (2011). Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats. Alcohol and Alcoholism, 46(3), 239-246.

Wood, D. A., Walker, T. L. & Rebec G.V. (2011). Experience-dependent changes in neuronal processing in the nucleus accumbens shell in a discriminative learning task in differentially housed rats. Brain Research, 1390, 90-98.

Walker, A.G., Ummel, J.R., & Rebec, G.V. (2011). Reduced expression of conditioned fear in the R6/2 mouse model of Huntington’s disease is related to abnormal activity in prelimbic cortex. Neurobiology of Disease, 43(2):379-387.

Miller, B.R., Dorner, J.L., Gaither, T.W., Klein, E.L., Barton, S.J., & Rebec, G.V. (2011). Dysregulated neuronal activity patterns implicate corticostriatal circuit dysfunction in multiple rodent models of Huntington’s disease. Frontiers in Systems Neuroscience, 5:26, 1-10.[www.frontiersin.org - May 2011]

Sari, Y., Prieto, A. L., Barton, S. J., Miller, B. R., & Rebec, G.V. (2010). Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6/2 model of Huntington’s disease. Journal of Biomedical Science, 17, 62 (1-5).

Ball, K. T., Wellman, C. L., Miller, B. R., and Rebec, G.V. (2010). Electrophysiological and structural alterations in striatum associated with behavioral sensitization to (±) 3,4-Methylenedioxymethamphetamine (Ecstasy) in rats: Role of drug context. Neuroscience, 171:794-811.

Miller, B. R., Walker, A. G., Fowler, S. C., von Hörsten, S., Riess, O., Johnson, M. A., & Rebec, G.V. (2010). Dysregulation of coordinated neuronal firing patterns in striatum of freely behaving transgenic rats that model Huntington’s disease. Neurobiology of Disease, 37(1):106-113.

Rebec, G.V. (2010). A central role for the periphery in the rapid action of cocaine on brain neurons: focus on "Rapid EEG desynchronization and EMG activation induced by intravenous cocaine in freely moving rats: peripheral, nondopamine neural triggering", Am J Physiol - Regulatory, Integrative and Comp Physiol, 298 (2):R283-284.

Sari, Y., Hammad, L. A. A., Saleh, M. M., Rebec, G.V., & Mechref, Y. (2010). Alteration of selective neurotransmitters in fetal brains of alcohol treated prenatally C57BL/6 mice: quantitative analysis using liquid chromatography/tandem mass spectrometry methods. International Journal of Developmental Neuroscience, 28:263-269.

Hall, I. C., Rebec, G.V., & Hurley, L. M. (2010). Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli. Journal of Experimental Biology, 213:1009-1017.

Wood, D. A. & Rebec, G.V. (2009). Environmental enrichment alters neuronal processing in the nucleus accumbens core during appetitive conditioning. Brain Research, 1259, 59-67.

Ball, K. T., Wellman, C. L., Fortenberry, E., & Rebec, G.V. (2009). Sensitizing regimens of MDMA (Ecstasy) elicit enduring and differential structural alterations in the brain motive circuit. Neuroscience, 60(2):264-274.

Fowler, S. C., Miller, B. R., Gaither, T. W., Johnson, M. A., & Rebec, G.V. (2009). Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease. Behavioural Brain Research, 202, 130-137.

Sari, Y, Smith, K. D., Ali, P. K., & Rebec, G.V. (2009). Up-regulation of GLT1 attenuates cue-induced reinstatement of cocaine seeking in rats. Journal of Neuroscience, 29(29):9239-9243.

Dorner, J.L, Miller, B.R., Klein, E.L., Murphy-Nakhnikian, A., Andrews, R.L., Barton, S.J., and Rebec, G.V. (in-press) Corticostriatal dysfunction underlies diminished striatal ascorbate release in the R6/2 mouse models of Huntington’s disease. Brain Research, in press.

Sari,Y., Smith, K.D., Ali, P.K., and Rebec, G.V. (2009) Up-regulation of GLT1 attenuates cue-induced reinstatement of cocaine seeking in rats. Journal of Neuroscience, [Epub July 22, 2009).

Fowler, S.C., Miller, B.R., Gaither, T.W., Johnson, M.A., and Rebec, G.V. (2009) Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease. Behavioural Brain Research, 202: 130-137.

Ball, K.T., Wellman, C.L., Fortenberry, E., and Rebec, G.V. (2009) Sensitizing regimens of MDMA (Ecstasy) elicit enduring and differential structural alterations in the brain motive circuit. Neuroscience, 2009, Feb. 21 [Epub ahead of print].

Wood, D.A. and Rebec, G.V. (2009) Environmental enrichment differentially alters neuronal processing in the nucleus accumbens core appetitive conditioning. Brain Research, 59-67.

Ball, K.T. and Rebec, G.V. (2008) Electrophysiological and Morphological Adaptations in Cortico-striato-limbic Circuitry Induced by 3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy). In: Nucleus Accumbens: Neurotransmitters and Related Behaviours, David, H. (ed.). Research Signpost: Kerala, India.

Walker, A.G., Miller, B.R., Fritsch, J.N., Barton, S.J., and Rebec, G.V. (2008) Altered information processing in the prefrontal cortex of Huntington’s disease mouse models. Journal of Neuroscience, 28(36):8973-8982.

Miller, B.R., Walker, A.G., Shah, A.S., Barton, S.J., and Rebec, G.V. (2008) Dysregulated information processing by medium-spiny neurons in striatum of freely behaving mouse models of Huntington’s disease. Journal of Neurophysiology, 100(4):2205-2216.

Miller, B.R., Dorner, J.L., Shou, M., Sari, Y., Barton, S.J., Sengelaub, D.R., Kennedy, R.T., and Rebec, G.V. (2008) Up-regulation of GLT1 expression increases glutamate uptake and improves the Huntington’s disease phenotype. Neuroscience, 153(1):329-337.

Sunsay, C. and Rebec, G.V. (2008) Real-time dopamine efflux in the nucleus accumbens core during Pavlovian conditioning. Behavioral Neuroscience, 122(2):358-367.

Ball, K.T., Walsh, K.M., and Rebec, G.V. (2007) Reinstatement of MDMA (ecstasy) seeking by exposure to drug-conditioned cues. Pharmacology, Biochemistry and Behavior. [Epub ahead of print - available online at www.sciencedirect.com ].

Sandstrom, M.I. and Rebec, G.V. (2007) Extracellular ascorbate modulates glutamate dynamics: role of behavioral activation. BMC Neuroscience, 8: 32.

Teagarden, M.A. and Rebec, G.V. (2007) Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task. Journal of Neurophysiology, 97: i>2042-2058.

Dorner, J.L., Miller, B.R., Barton, S.J., Brock, Tyler J., and Rebec, G.V. (2007) Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington’s disease. Behavioural Brain Research, 178: 90-97.

Rebec, G.V. (2007) From interferant anion to neuromodulator: ascorbate oxidizes its way to respectability. In: Electrochemical Methods in Neuroscience, Taylor & Francis Group, CRC Press, Boca Raton, FL.

Rebec, G.V. (2006) Behavioral electrophysiology of psychostimulants. Neuropsychopharmacology, 31 (11): 2341-2348.

Sun, W.L. and Rebec, G.V. (2006) Repeated cocaine self-administration alters processing of cocaine-related information in rat prefrontal cortex. Journal of Neuroscience, 26: 8004-8008.

Ball, K.T., Budreau, D., and Rebec, G.V. (2006) Context-dependent behavioral and neuronal sensitization in striatum to MDMA (ecstasy) administration in rats. European Journal of Neuroscience, 24: 217-228.

Wood, D.A., Siegel, A.K., and Rebec, G.V. (2006) Environmental enrichment reduces impulsivity during appetitive conditioning. Physiology and Behavior, 88(1-2): 132-137.

Rebec, G.V., Conroy, S.K., Barton, S.J. (2006) Hyperactive striatal neurons in symptomatic Huntington R6/2 mice: Variations with behavioral state and repeated ascorbate treatment. Neuroscience, 137: 327-336.

Rebec, G.V. and Sun, W.L. (2005) Neuronal substrates of relapse to cocaine-seeking behavior: role of prefrontal cortex. Journal of the Experimental Analysis of Behavior, 84(3): 653-666.

Sun, W.L., Akins, C.K., Mattingly, A.E., and Rebec, G.V. (2005) Ionotropic glutamate receptors in the ventral tegmental area regulate cocaine-seeking behavior in rats. Neuropsychopharmacology,30: 2073-2081.

Wood, D.A., Buse, J.E., Wellman, C.L., and Rebec, G.V. (2005) Differential environmental exposure alters NMDA but not AMPA receptor subunit expression in nucleus accumbens core and shell. Brain Research, 1042: 176-183.

Rebec, G.V., Witowski, S.R., Sandstrom, M.I., Rostand, R.D., and Kennedy, R.T. (2005) Extracellular ascorbate modulates cortically evoked glutamate dynamics in rat striatum. Neuroscience Letters, 378: 166-170.

Sun, W.L. and Rebec, G.V. (2005) The role of prefrontal cortex D1-lik,e and D2-like receptors in cocaine-seeking behavior in rats. Psychopharmacology, 177: 315-323.

Sun, W.L. and Rebec, G.V. (2003) Lidocaine inactivation of ventral subiculum attenuates cocaine-seeking behavior in rats. Journal of Neuroscience, 23: 10258-10264.

Garris, P.A. and Rebec, G.V. (2002) Modeling fast dopamine neurotransmission in the nucleus accumbens during behavior. Behavioural Brain Research, 137: 47-63.

Rebec, G.V., Barton, S.J., and Ennis, M.D. (2002) Dysregulation of ascorbate in the striatum of behaving mice expressing the Huntington’s disease gene. Journal of Neuroscience, 22: RC202 (1-5).

Rebec, G.V. and Wang, Z. (2001)Behavioral activation in rats require endogenous ascorbate release in striatum. Journal of Neuroscience, 21: 668-675.

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