Rodrigo Andrade, Ph.D.
Rodrigo Andrade, Ph.D.
Research in the Andrade lab focuses on on the mechanisms underlying neuronal communication/synaptic transmission in the brain. Specifically our work seeks to elucidate the molecular mechanisms whereby neurotransmitters acting via G protein coupled receptors (GPCRs) signal their responses in neurons of the central nervous system.
Over the years we have focused principally on GPCRs sensing serotonin and secondarily acetylcholine, primarily in hippocampus and prefrontal cortex. Initially our work relied on pharmacological approaches in combination with electrophysiology, when that was all that was available. More recently we have fused these with imaging, molecular and genetic approaches to elucidate the role of specific genes and proteins in generating the physiology of CNS neurons. Most recently, with the advent of optogenetics we have become very interested in the physiology of synapses using GPCRs, which is the natural extension in the physiological direction of our previous work. The long term goal of this effort is to contribute to a mechanistic understanding of the pathophysiology of mental disorders while simultaneously contributing to the development of better therapeutic approaches. We have been fortunate to have our work funded by the NIH, for which we are very grateful.
Serotonin in the hippocampus. During the 1980s and 1990s work from many labs helped define a large family of GPCRs sensing serotonin. At the time very little was known about how these channels regulated neuronal physiology. First as a postdoc and then in my own lab we defined the physiological effects of serotonin in pyramidal cells of the CA1 region, identified the serotonin receptor subtypes involved, and elucidates their signaling mechanism. These results contributed to our understanding of the physiology and pharmacology of the 5-HT1A and 5-HT4 receptors.
Andrade, R., R.C. Malenka and R.A. Nicoll (1986) A G-protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 234:1261-1265.
Andrade, R. and R.A. Nicoll (1987) Pharmacologically distinct actions of serotonin on single pyramidal neurons of the rat hippocampus recorded in vitro. J. Physiol (London) 394:88-124.
Andrade, R. (1993) Enhancement of -adrenergic responses by Gi linked receptors in rat hippocampus, Neuron. 10:83-88.
Torres, G.E., Chaput, Y. and R. Andrade (1995) cAMP and PKA mediate 5-HT4 receptor regulation of calcium-activated potassium current in adult hippocampal neurons, Molecular Pharmacol. 47:191-197.
Serotonin in the prefrontal cortex. Our work in hippocampus provided only a partial glimpse at the diversity of serotonin receptors. Therefore we extended our work to the prefrontal cortex, which expresses a different complement of serotonin receptors and we felt was more central to the pathophysiology of mental disorders. Working in this region we were able identify functional roles for 5-HT1A, 5-HT2A and 5-HT7 receptors in adults and during development and begin mapping their signaling mechanisms.
Araneda, R. and R. Andrade (1990) 5-HT2 and 5-HT 1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neurosci. 40:399-412.
Beique J.-C., Campbell, B., Perring, P., Hamblin, M., Walker, P., L. Mladenovic and R. Andrade (2004) Serotonergic regulation of membrane potential in developing rat prefrontal cortex: Coordinated expression of 5-HT1A, 5-HT2A and 5-HT7 receptors. J. Neurosci. 24:4807-17.
Béïque J.-C., Imad, M., Mladenovic L., Gingrich J.A. and R. Andrade (2007) Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proc. Natl. Acad. Sci. (USA) 104:9870-9875.
Weber, E.T. and R. Andrade (2010) Htr2a gene and 5-HT2A receptor expression in the cerebral cortex studied using genetically modified mice. Front Neurosci 4:36. doi:10.3389/fnins.2010.00036
Gaq-11 signaling in prefrontal cortex and the slow afterdepolarization. Our work on 5-HT2A receptors in prefrontal cortex led us to focus more broadly on effects signaled by Gaq-11 –coupled receptors, whose physiology was understood only very partially at the time. This resulted in the identification of responses mediated by non-selective cation channels and especially in the “rediscovery” (with two other labs) of a phenomenon known as the slow afterdepolarization (sADP). This is a fascinating phenomenon that is triggered by activation of Gaq-11 –coupled receptors and allow cells to undergo sustained changes in excitability greatly outlasting the initial stimulus. These phenomena is now known to be widespread in the brain.
Andrade, R. (1991) Cell excitation enhances muscarinic cholinergic responses in rat association cortex. Brain Res. 548:81-93.
Haj-Dahmane, S. and R. Andrade (1996) Carbachol activates a voltage dependent cation current in rat prefrontal cortex, J. Neurosci., 16:3848-3861.
Haj-Dahmane, S. and R. Andrade (1997) A calcium-activated cation nonselective current in rat prefrontal cortex, J. Neurophysiol. 78:1983-1989.
Yan, H.-D., Villalobos C. and R. Andrade (2009) TRPC channels mediate a muscarinic receptor-induced afterdepolarization in cerebral cortex. J, Neurosci., 29:10038-46
The slow afterhyperpolarization. Work starting in the 1980s identified a phenomenon known as the slow afterhyperpolarization (sAHP) as a ubiquitous target for regulation by multiple classes of G protein coupled receptors in the brain. This phenomenon proved remarkably resistant to mechanistic analysis for many years. We have worked on this phenomenon since the 1980s (starting as a grad student!) and have contributed to the elucidation of key aspects of its physiology. Most recently we have developed a model that we believe finally explains this phenomenon and why it may have resisted mechanistic analysis for so long.
Villalobos, C., Shakkottai, V., Chandy, G., Michelhaugh, S. and R. Andrade (2004) SKCa channels mediate the medium but not the slow calcium-activated afterhyperpolarization in cortical neurons. J. Neurosci.24: 3537-3542
Villalobos, C. and R. Andrade (2010) Visinin-like neuronal calcium sensor proteins regulate the slow calcium-activated afterhyperpolarizing current in the rat cerebral cortex. J. Neurosci. 30:14361-14365.
Villalobos, C, Foehring, R.C., Lee, J.C. and R. Andrade (2011) Essential role for PtdIns(4,5)P2 in the expression and regulation of the slow calcium-activated afterhyperpolarizing current in the cerebral cortex. J. Neurosci. 31:18303-12.
Andrade R., Foehring R.C. and Tzingounis A.V. (2012) The calcium-activated slow AHP: cutting through the Gordian knot. Front. Cell. Neurosci. 6:47.doi: 10.3389/fncel.2012.00047
Dallas Khamiss, B.A. Research Assistant
Elaine T. Andrade, M.S., Lab Manager
Ricardo C. Araneda, PhD. 1988-1991. Currently Assistant Professor, Dept. of Biology, University of Maryland.
Gonzalo E. Torres, PhD. 1993-1996. Currently Associate Professor, Dept of Neurobiology, Univ of Pittsburg.
James E. Cooper, M.D. 1997- 1999. Currently Assistant Professor, University of Colorado School of Medicine.
Paul D. Perring, M.D. 2000-2002. Currently in clinical practice at ProMedica Anesthesiology Consultants, Ohio.
Mary Elliott, B.S. 2009-2010. Currently medical student at Michigan State University
Daniel Wyskiel, B.S. 2010-2011. Currently Neuroscience PhD student at the University of Virginia.
Peter Tanaka, B.S. 2010-2012. Currently studying life in Dublin, Ireland
Alicia Aleardi, B.S. 2012-2013. Currently medical student at Central Michigan University.
Esther Penick (nee Chapin). PhD, Cellular and Clinical Neurobiology, 2000. Currently Associate Professor, Department of Biology, Knox College.
Mays Imad. PhD, Cellular and Clinical Neurobiology, 2006. Currently Post doctoral fellow, Department of Neuroscience, University of Arizona.
Claudio Villalobos. PhD, Pharmacology, 2010. Currently Postdoctoral fellow, Instituto de Ciencias Biomedicas, Faculty of Medicine, University of Chile.
Kelly McGregor, Ph.D. Pharmacology, 2015.
Yves Chaput, MD. 1988-1990. Professor, School of Medicine, McGill University (now retired from academic life).
Samir Haj-Dahmane, PhD. 1993-1997. Currently Principal Investigator, Research Institute on Addictions, University of Buffalo.
Roh-Yu Chen, PhD. 1996-1997. Currently Principal Investigator, Research Institute on Addictions, University of Buffalo.
Jean-Claude Beique, Ph.D. 2000-2004. Currently Assistant Professor, Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa.
Hai-Dun Yan, PhD. 2002-2005. Currently Research Scientist, Ion Channel Research Unit, Duke University School of Medicine.
Dr. Andrade is no longer taking PhD students.
B.A. Biology, Kalamazoo College, Kalamazoo, MI. 1977
Ph.D, Pharmacology. Yale University, New Haven, CT. 1984
Links of Interest
- Beique J.-C., Imad, M, L. Mladenovic, Gingrich, J.A. and R. Andrade (2007) Mechanism of 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proc. Natl Acad Sci USA 104: 9870-9875.
- Yan, H.-D., Villalobos C. and R. Andrade (2009) TRPC channels mediate a muscarinic receptor-induced afterdepolarization in cerebral cortex. J, Neurosci., 29:10038-46.
- Villalobos, C. and R. Andrade (2010) Visinin-like neuronal calcium sensor proteins regulate the slow calcium-activated afterhyperpolarizing current in the rat cerebral cortex. J. Neurosci, 30:14361-14365.
- Villalobos, C, Foehring, R.C., Lee, J.C. and R. Andrade (2011) Essential role for PtdIns(4,5)P2 in the expression and regulation of the slow calcium-activated afterhyperpolarizing current in the cerebral cortex. J. Neurosci. 31:18303-12.
- Andrade R., Foehring R.C. and Tzingounis A.V. (2012) The calcium-activated slow AHP: cutting through the Gordian knot. Front. Cell. Neurosci. 6:47.doi: 10.3389/fncel.2012.00047 (review)