Cellular and Molecular Pharmacology Discipline

Stanson Toshok Center for Brain Function and Repair

Heinz Steiner graduated from the Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland with an M.S. in Biology. He earned his PhD degree in Physiological Psychology from the University of Dusseldorf (Germany) in 1989. Following postdoctoral work at the Laboratory of Cell Biology and Laboratory of Neurophysiology of the National Institute of Mental Health, Bethesda, MD, he was appointed in 1995 as a Research Assistant Professor in the Department of Anatomy and Neurobiology at The University of Tennessee, College of Medicine, and The Center for Neuroscience in Memphis, TN. He joined the Chicago Medical School faculty in 2000 in the Cellular and Molecular Pharmacology discipline, and he was appointed discipline chair in 2011.

Research

Our research focuses on the functional organization of the basal ganglia and related brain systems, especially on the role of the neurotransmitter dopamine in the regulation of basal ganglia - cortical interactions. One of the main objectives is to understand how pathologically altered activities in transmitter systems such as dopamine cause neuroadaptive changes in neurons of the basal ganglia and their functional consequences. Current projects investigate how chronic enhancement of dopamine actions [e.g., by psychostimulants such as cocaine and methylphenidate (Ritalin)], or their attenuation (e.g., by antipsychotic drugs or dopamine depletion), produce changes in gene regulation, and how these molecular alterations affect basal ganglia function and behavior. Genes encoding neuropeptide transmitters (e.g., opioid peptides), enzymes, receptors, ion channels, transcription factors, and other plasticity-associated molecules are of primary interest. Some of the current studies investigate drug effects on molecular and cellular mechanisms of motor learning.

These questions are mainly studied in the following animal models: 1) repeated treatment with dopamine agonists (e.g., psychostimulants) or antagonists (e.g., antipsychotics) in rats; 2) dopamine depletion by neurotoxins (models for Parkinson's disease) in rats; and 3) in mice with null mutations for specific receptors or neuropeptides (gene knockouts). Gene expression is measured with quantitative in situ hybridization histochemistry in combination with autoradiography and immunohistochemical techniques. Other experimental approaches include anatomical techniques (e.g., tract tracing, ultrastructural imaging) and electrophysiological methods (in collaboration). In many of our studies, molecular/cellular and behavioral effects are measured in parallel for correlation analyses.

Edited Books

Handbook of Basal Ganglia Structure and Function, Handbook of Behavioral Neuroscience Series, Volumes 20 & 24, Academic Press/Elsevier, London.

The Basal Ganglia comprise a group of forebrain nuclei that are interconnected with the cerebral cortex, thalamus and brainstem. Basal ganglia circuits are involved in various functions, including motor control and learning, sensorimotor integration, reward and cognition. The importance of these nuclei for normal brain function and behavior is emphasized by the numerous and diverse disorders associated with basal ganglia dysfunction, including Parkinson’s disease, Tourette’s syndrome, Huntington’s disease, obsessive-compulsive disorder, dystonia, and psychostimulant addiction.

The Handbook of Basal Ganglia Structure and Function first edition (2010; 39 chapters, 704p.) provides an overview of the organization of the basal ganglia, emphasizing progress achieved over the last 10-15 years. Authored by internationally acclaimed basal ganglia researchers, this volume describes the anatomical organization and reviews molecular, cellular and physiological mechanisms, as well as behavioral and clinical aspects of the basal ganglia.

The second edition (2016; 49 chapters, 1036p.) has been thoroughly revised to provide the most up-to-date account of this critical brain structure. The new edition contains twenty entirely new chapters that review evolution and history of the basal ganglia, and offer expanded coverage of anatomy and physiology, and detailed accounts of recent advances and deeper insights into the behavioral and clinical aspects of basal ganglia function and dysfunction.

Publications

Altwal, F., Moon, C., West, A.R., and Steiner, H., The multimodal serotonergic agent Vilazodone inhibits L-DOPA-induced gene regulation in striatal projection neurons and associated dyskinesia in an animal model of Parkinson's disease. Cells 9:2265, 2020.

Padovan-Neto, F.E., Patterson, S., Voelkner, N.M.F., Altwal, F., Beverley, J.A., West, A.R., and Steiner, H.,  Selective regulation of 5-HT1B serotonin receptor expression in the striatum by dopamine depletion and repeated L-DOPA treatment: Relationship to L-DOPA-induced dyskinesias.  Mol. Neurobiol. 57:736-751, 2020.

Alter, D., Beverley, J.A., Patel, R., Bolaños-Guzmán, C.A., and Steiner, H., The 5-HT1B serotonin receptor regulates methylphenidate-induced gene expression in the striatum: Differential effects on immediate-early genes. J. Psychopharmacol. 31:1078-1087, 2017.

Pedron, S., Beverley, J., Haffen, E., Andrieu, P., Steiner, H. and Van Waes, V., Transcranial direct current stimulation produces long-lasting attenuation of cocaine-induced behavioral responses and gene regulation in corticostriatal circuits. Addict. Biol. 22:1267-1278, 2017.

Steiner, H., Psychostimulant-induced gene regulation in striatal circuits. In: Handbook of Basal Ganglia Structure and Function, Second Edition; H. Steiner and K.Y. Tseng (Eds.); Handbook of Behavioral Neuroscience Series, Vol. 24; Academic Press/Elsevier, London, pp. 639-672, 2016.

Trossbach, S.V., Bader, V., Hecher, L., Pum, M.E., Masoud, S.T., Prikulis, I., Schäble, S., de Souza Silva, M.A., Su, P., Boulat, B., Chwiesko, C., Poschmann, G., Stühler, K., Lohr, K.M., Stout, K.A., Weisshaupt, A., Godsave, S.F., Müller-Schiffmann, K., Bilzer, T., Steiner, H., Peters, P.J., Bauer, A., Sauvage, M., Ramsey, A.J., Miller, G.W., Liu, F., Seeman, P., Brandon, N.J., Huston, J.P. and Korth, C., Misassembly of full-length Disrupted-in-Schizophrenia 1 protein is linked to altered dopamine homeostasis and behavioral deficits. Molecular Psychiatry 21:1561-1572, 2016.

Van Waes, V. and Steiner, H., Fluoxetine and other SSRI antidepressants potentiate addiction-related gene regulation by psychostimulant medications. In: Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects, G. Pinna (Ed.), Nova Science Publishers, New York, pp. 207-225, 2015.

Van Waes, V., Ehrlich, S., Beverley, J.A. and Steiner, H., Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: Potential role for 5-HT1B receptor. Neuropharmacology 89:77-86, 2015.

Beverley, J.A., Piekarski, C., Van Waes, V. and Steiner, H., Potentiated gene regulation by methylphenidate plus fluoxetine treatment: Long-term gene blunting (Zif268, Homer1a) and behavioral correlates. Basal Ganglia 4:109-116, 2014.

Van Waes, V., Vandrevala, M., Beverley, J. and Steiner, H., Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a. Addict. Biol. 19:986–995, 2014.

Steiner, H., Warren, B.L., Van Waes, V. and Bolaños-Guzmán, C.A., Life-long consequences of juvenile exposure to psychotropic drugs on brain and behavior. Prog. Brain Res. 211:13-30, 2014.

Unterwald, E.M., Page, M.E., Brown, T.B., Miller, J.S., Ruiz, M., Pescatore, K.A., Xu, B., Reichardt, L.F., Beverley, J., Tang, B., Steiner, H., Thomas, E.A. and Ehrlich, M.E., Behavioral and transcriptome alterations in male and female mice with postnatal deletion of TrkB in dorsal striatal medium spiny neurons. Mol. Neurodegener. 8:47, 2013.

Steiner, H., LRRKing up the right trees? On figuring out the effects of mutant LRRK2 and other Parkinson's disease-related genes. Basal Ganglia 3:73-76, 2013 (editorial).

Steiner, H. and Van Waes, V., Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants. Prog. Neurobiol. 100:60-80, 2013.

Van Waes, V., Carr, B., Beverley, J.A. and Steiner, H., Fluoxetine potentiation of methylphenidate-induced neuropeptide expression in the striatum occurs selectively in direct pathway (striatonigral) neurons. J. Neurochem. 122:1054-1064, 2012.

Van Waes, V., Beverley, J. A., Siman, H., Tseng, K. Y. and Steiner, H., CB1 cannabinoid receptor expression in the striatum: association with corticostriatal circuits and developmental regulation. Front. Pharmacol. 3:21, 2012.

Steiner, H., Basal Ganglia - A Willisian journal. Basal Ganglia 1:175-176, 2011 (editorial).

Van Waes, V., Tseng, K. Y. and Steiner, H., GPR88 - a putative signaling molecule predominantly expressed in the striatum: Cellular localization and developmental regulation. Basal Ganglia 1:83-89, 2011.

Heng, L., Beverley, J. A., Steiner, H. and Tseng, K. Y., Differential developmental trajectories for CB1 cannabinoid receptor expression in limbic/associative and sensorimotor cortical areas. Synapse 65:278-286, 2011.

Ondracek, J. M., Willuhn, I., Steiner, H. and West, A. R., Interactions between procedural learning and cocaine exposure alter spontaneous and cortically evoked spike activity in the dorsal striatum. Front. Neurosci. 4:206, 2010.

Van Waes, V., Beverley, J., Marinelli, M. and Steiner, H., Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum. Eur. J. Neurosci. 32:435-447, 2010.

Steiner, H., Psychostimulant-induced gene regulation in corticostriatal circuits. In: Handbook of Basal Ganglia Structure and Function, H. Steiner and K. Y. Tseng (Eds.), Handbook of Behavioral Neuroscience Series, Vol. 20; Elsevier, London, pp. 501-525, 2010.

Steiner, H., Van Waes, V. and Marinelli, M., Fluoxetine potentiates methylphenidate-induced gene regulation in addiction-related brain regions: Concerns for use of cognitive enhancers? Biol. Psychiatry 67:592-594, 2010.

Willuhn, I. and Steiner, H., Motor-skill learning in a novel running-wheel paradigm: Long-term memory consolidation by D1 receptors in the striatum. In: The Basal Ganglia IX, H. J. Groenewegen et al. (Eds.), Springer, Berlin, pp. 255-267, 2009.

Unal, C. T., Beverley, J. A., Willuhn, I. and Steiner, H., Long-lasting dysregulation of gene expression in corticostriatal circuits after repeated cocaine treatment in adult rats: effects on zif 268 and homer 1a. Eur. J. Neurosci. 29:1615-1626, 2009.

Willuhn, I. and Steiner, H., Skill-memory consolidation in the striatum: Critical for late but not early long-term memory and stabilized by cocaine. Behav. Brain Res. 199:103-107, 2009.

Willuhn, I. and Steiner, H., Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum. Neuroscience 153:249-258, 2008.

Tropea, T. F., Guerriero, R. M., Willuhn, I., Unterwald, E. M., Ehrlich, M. E., Steiner, H. and Kosofsky, B. E., Augmented D1 dopamine receptor signaling and immediate-early gene induction in adult striatum following prenatal cocaine. Biol. Psychiatry 63:1066-1074, 2008.

Yano, M. and Steiner, H., Methylphenidate and cocaine: the same effects on gene regulation? Trends Pharmacol. Sci. 28:588-596, 2007.

Steiner, H., Basal ganglia – cortex interactions: Regulation of cortical function by D1 dopamine receptors in the striatum. In: Monoaminergic Modulation of Cortical Excitability, K. Y. Tseng and M. Atzori (Eds.), Springer, Berlin, pp. 265-285, 2007.

Cotterly, L., Beverley, J. A., Yano, M. and Steiner, H., Dysregulation of gene induction in corticostriatal circuits after repeated methylphenidate treatment in adolescent rats: Differential effects on zif 268 and homer 1a. Eur. J. Neurosci. 25:3617-3628, 2007.

Yano, M., Beverley, J. A. and Steiner, H., Inhibition of methylphenidate-induced gene expression in the striatum by local blockade of D1 dopamine receptors: interhemispheric effects. Neuroscience 140:699-709, 2006.

Willuhn, I. and Steiner, H., Motor-skill learning-associated gene regulation in the striatum: Effects of cocaine. Neuropsychopharmacology 31:2669-2682, 2006.

Meredith, G. E. and Steiner, H., Amphetamine increases tyrosine kinase-B receptor expression in the dorsal striatum. Neuroreport 17:75-78, 2006.

Willuhn, I. and Steiner, H., Motor learning-related gene regulation in the striatum: Effects of cocaine. In: The Basal Ganglia VIII, J. P. Bolam et al. (Eds.), Springer, Berlin, pp. 197-207, 2005.

Yano, M. and Steiner, H., Methylphenidate (Ritalin) induces expression of Homer 1a and zif 268 in specific corticostriatal circuits. Neuroscience 132:855-865, 2005.

Yano, M. and Steiner, H., Topography of methylphenidate (Ritalin)-induced gene regulation in the striatum: Differential effects on c-fos, substance P and opioid peptides. Neuropsychopharmacology 30:901-915, 2005.

Brandon, C. L. and Steiner, H., Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum. Eur. J. Neurosci. 18:1584-1592, 2003.

Willuhn, I., Sun, W. and Steiner, H., Topography of cocaine-induced gene regulation in the rat striatum: Relationship to cortical inputs and role of behavioural context. Eur. J. Neurosci. 17:1053-1066, 2003.

Steiner, H. and Kitai, S. T., Unilateral striatal dopamine depletion: time-dependent effects on cortical function and behavioural correlates. Eur. J. Neurosci. 14:1390-1404, 2001.

Carta, A. R., Gerfen, C. R. and Steiner, H., Cocaine effects on gene regulation in the striatum and behavior: Increased sensitivity in D3 dopamine receptor-deficient mice. Neuroreport 11:2395-2399, 2000.

Steiner, H. and Kitai, S. T., Regulation of rat cortex function by D1 dopamine receptors in the striatum. J. Neurosci. 20:5449-5460, 2000.

Steiner, H., Blum, M., Kitai, S. T. and Fedi, P., Differential expression of ErbB3 and ErbB4 neuregulin receptors in dopamine neurons and forebrain areas of the adult rat. Exp. Neurol. 159:494-503, 1999.

Steiner, H. and Gerfen, C. R., Enkephalin regulates acute D2 dopamine receptor antagonist-induced immediate-early gene expression in striatal neurons. Neuroscience 88:795-810, 1999.

Steiner, H., Bonner, T. I., Zimmer, A. M., Kitai, S. T. and Zimmer, A., Altered gene expression in striatal projection neurons in CB1 cannabinoid receptor knockout mice. Proc. Natl. Acad. Sci. USA 96:5786-5790, 1999.

Steiner, H. and Gerfen, C. R., Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior. Exp. Brain Res. 123:60-76, 1998.

Gerfen, C. R., Keefe, K. A. and Steiner, H., Dopamine-mediated gene regulation in the striatum. Adv. Pharmacol. 42:670-673, 1998.

Steiner, H., Fuchs, S. and Accili, D., D3 dopamine receptor-deficient mouse: evidence for reduced anxiety. Physiol. Behav. 63:137-141, 1998.

Melzer, P. and Steiner, H., Stimulus-dependent expression of immediate-early genes in rat somatosensory cortex. J. Comp. Neurol. 380:145-153, 1997.

Steiner, H. and Gerfen, C. R., Dynorphin regulates D1 dopamine receptor-mediated responses in the striatum: relative contributions of pre- and postsynaptic mechanisms in dorsal and ventral striatum demonstrated by altered immediate-early gene induction. J. Comp. Neurol. 376:530-541, 1996.

Konig, M., Zimmer, A. M., Steiner, H., Holmes, P. V., Crawley, J. N., Brownstein, M. J. and Zimmer, A., Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature 383:535-538, 1996.

Drago, J., Gerfen, C. R., Westphal, H. and Steiner, H., D1 dopamine receptor-deficient mouse: cocaine-induced regulation of immediate-early gene and substance P expression in the striatum. Neuroscience 74:813-823, 1996.

Accili, D., Fishburn, C. S., Drago, J., Steiner, H., Lachowicz, J. E., Park, B. H., Gauda, E. B., Lee, E. J., Cool, M. H., Sibley, D. R., Gerfen, C. R., Westphal, H. and Fuchs S., A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proc. Natl. Acad. Sci. USA 93:1945-1949, 1996.