Douglas G. McMahon, Ph.D.

Professor

douglas.g.mcmahon@vanderbilt.edu

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Faculty Appointments
Professor of Biological Sciences Stevenson Chair in Biological SciencesProfessor of Ophthalmology & Visual SciencesProfessor of Pharmacology
Education
Ph.D., Molecular Neurobiology , University of Virginia, Charlottesville, VirginiaB.A., BIOLOGY, University of Virginia, Charlottesville, Virginia
Office Address
VU Station B, Box 35-1634
Nashville, TN 37235-1634
Research Description
Broadly stated, our lab is interested in neural plasticity - the relatively slow and sustained changes in neural function that result from the interplay of ionic, chemical and genetic signaling in neural circuits of the brain. Our research concentrates on the mechanisms of plasticity as they are expressed in three linked subsystems of the central nervous system - the visual, circadian, and serotonergic systems that mediate our sense of sight, drive our daily rhythms, and influence our mood. Specifically, our research targets key populations of neurons that regulate platicity through release of the modulatory biogenic amine transmitters, dopamine and serotonin, or that generate endogenous daily rhythms through gene-driven processes within neurons. Mechanistically, we focus on synaptic ion channel signaling and how it is influenced by interneuronal modulation, the regulation of autonomous neuronal activity for neurosecretion and circadian rhythms, and gene expression dynamics as a functional measure of neural activity in living neuronal ensembles.

In addressing the cellular, molecular, and genetic mechanisms of dopaminergic, serotonergic, and biological clock neurons, our research provides basic knowledge relevant to a wide range of neurological disorders, including dopaminergic disorders, such as Parkinsonism, schizophrenia and addiction; circadian disorders, such as winter depression and sleep phase syndromes; serotonergic disorders, such as photoreceptor degeneration and myopia.

Our laboratory takes a multidisciplinary approach, combining experiments at the behavioral, cellular, molecular, and genetic levels to uncover novel neural mechanisms that govern vision, biological rhythms, and mood. As our primary research organisms, we use two vertebrate model systems, in which the genome is readily manipulated, the mouse and the zebrafish, in order to facilitate the use of reporter gene animals, as well as gene knock-outs, knock-ins, and mutants. An overarching theme in our lab is the use of reporter animals, which harbor fluorescent or luminescent reporter transgenes that identify specific neuron populations or report the dynamics of gene expression in living tissue. Our laboratory has been at the forefront of developing both reporter mouse models and the imaging and physiological techniques for their use.
Research Keywords
Molecular neurobiology of the visual, circadian, and serotonergic systems and their interactions.
Publications
Dai Y, Carlin KP, Li Z, McMahon DG, Brownstone RM, Jordan LM. Electrophysiological and pharmacological properties of locomotor activity-related neurons in cfos-EGFP mice. J. Neurophysiol [print-electronic]. 2009 Dec; 102(6): 3365-83. PMID: 19793882, PMCID: PMC2804412, PII: 00265.2009, DOI: 10.1152/jn.00265.2009, ISSN: 1522-1598.

Sun Z, Zhang DQ, McMahon DG. Zinc modulation of hemi-gap-junction channel currents in retinal horizontal cells. J. Neurophysiol [print-electronic]. 2009 Apr; 101(4): 1774-80. PMID: 19176613, PMCID: PMC2695647, PII: 90581.2008, DOI: 10.1152/jn.90581.2008, ISSN: 0022-3077.

Ciarleglio CM, Gamble KL, Axley JC, Strauss BR, Cohen JY, Colwell CS, McMahon DG. Population encoding by circadian clock neurons organizes circadian behavior. J. Neurosci. 2009 Feb 2/11/2009; 29(6): 1670-6. PMID: 19211874, PMCID: PMC2670758, PII: 29/6/1670, DOI: 10.1523/JNEUROSCI.3801-08.2009, ISSN: 1529-2401.

Ruan GX, Allen GC, Yamazaki S, McMahon DG. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA. PLoS Biol. 2008 Oct 10/14/2008; 6(10): e249. PMID: 18959477, PMCID: PMC2567003, PII: 08-PLBI-RA-1447, DOI: 10.1371/journal.pbio.0060249, ISSN: 1545-7885.

Zhang DQ, Wong KY, Sollars PJ, Berson DM, Pickard GE, McMahon DG. Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Sep 9/16/2008; 105(37): 14181-6. PMID: 18779590, PMCID: PMC2544598, PII: 0803893105, DOI: 10.1073/pnas.0803893105, ISSN: 1091-6490.

Ciarleglio CM, Ryckman KK, Servick SV, Hida A, Robbins S, Wells N, Hicks J, Larson SA, Wiedermann JP, Carver K, Hamilton N, Kidd KK, Kidd JR, Smith JR, Friedlaender J, McMahon DG, Williams SM, Summar ML, Johnson CH. Genetic differences in human circadian clock genes among worldwide populations. J. Biol. Rhythms. 2008 Aug; 23(4): 330-40. PMID: 18663240, PMCID: PMC2579796, PII: 23/4/330, DOI: 10.1177/0748730408320284, ISSN: 0748-7304.

Hughes AT, Guilding C, Lennox L, Samuels RE, McMahon DG, Piggins HD. Live imaging of altered period1 expression in the suprachiasmatic nuclei of Vipr2-/- mice. J. Neurochem [print-electronic]. 2008 Aug; 106(4): 1646-57. PMID: 18554318, PMCID: PMC2658715, PII: JNC5520, DOI: 10.1111/j.1471-4159.2008.05520.x, ISSN: 1471-4159.

Meng S, Ryu S, Zhao B, Zhang DQ, Driever W, McMahon DG. Targeting retinal dopaminergic neurons in tyrosine hydroxylase-driven green fluorescent protein transgenic zebrafish. Mol. Vis [print-electronic]. 2008; 14: 2475-83. PMID: 19112533, PMCID: PMC2610293, ISSN: 1090-0535.

Gamble KL, Allen GC, Zhou T, McMahon DG. Gastrin-releasing peptide mediates light-like resetting of the suprachiasmatic nucleus circadian pacemaker through cAMP response element-binding protein and Per1 activation. J. Neurosci. 2007 Oct 10/31/2007; 27(44): 12078-87. PMID: 17978049, PII: 27/44/12078, DOI: 10.1523/JNEUROSCI.1109-07.2007, ISSN: 1529-2401.

Zhang DQ, Zhou TR, McMahon DG. Functional heterogeneity of retinal dopaminergic neurons underlying their multiple roles in vision. J. Neurosci. 2007 Jan 1/17/2007; 27(3): 692-9. PMID: 17234601, PII: 27/3/692, DOI: 10.1523/JNEUROSCI.4478-06.2007, ISSN: 1529-2401.

Kuhlman SJ, McMahon DG. Encoding the ins and outs of circadian pacemaking. J. Biol. Rhythms. 2006 Dec; 21(6): 470-81. PMID: 17107937, PII: 21/6/470, DOI: 10.1177/0748730406294316, ISSN: 0748-7304.

Zhang DQ, Sun Z, McMahon DG. Modulation of A-type potassium currents in retinal horizontal cells by extracellular calcium and zinc. Vis. Neurosci. 2006 Sep; 23(5): 825-32. PMID: 17020637, PII: S0952523806239993, DOI: 10.1017/S0952523806239993, ISSN: 0952-5238.

Ohta H, Mitchell AC, McMahon DG. Constant light disrupts the developing mouse biological clock. Pediatr. Res [print-electronic]. 2006 Sep; 60(3): 304-8. PMID: 16857759, PII: 01.pdr.0000233114.18403.66, DOI: 10.1203/01.pdr.0000233114.18403.66, ISSN: 0031-3998.

Fog JU, Khoshbouei H, Holy M, Owens WA, Vaegter CB, Sen N, Nikandrova Y, Bowton E, McMahon DG, Colbran RJ, Daws LC, Sitte HH, Javitch JA, Galli A, Gether U. Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport. Neuron. 2006 Aug 8/17/2006; 51(4): 417-29. PMID: 16908408, PII: S0896-6273(06)00508-3, DOI: 10.1016/j.neuron.2006.06.028, ISSN: 0896-6273.

Ruan GX, Zhang DQ, Zhou T, Yamazaki S, McMahon DG. Circadian organization of the mammalian retina. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2006 Jun 6/20/2006; 103(25): 9703-8. PMID: 16766660, PMCID: PMC1480470, PII: 0601940103, DOI: 10.1073/pnas.0601940103, ISSN: 0027-8424.

Maywood ES, Reddy AB, Wong GK, O'Neill JS, O'Brien JA, McMahon DG, Harmar AJ, Okamura H, Hastings MH. Synchronization and maintenance of timekeeping in suprachiasmatic circadian clock cells by neuropeptidergic signaling. Curr. Biol. 2006 Mar 3/21/2006; 16(6): 599-605. PMID: 16546085, PII: S0960-9822(06)01173-0, DOI: 10.1016/j.cub.2006.02.023, ISSN: 0960-9822.

Pitts GR, Ohta H, McMahon DG. Daily rhythmicity of large-conductance Ca2+ -activated K+ currents in suprachiasmatic nucleus neurons. Brain Res [print-electronic]. 2006 Feb 2/3/2006; 1071(1): 54-62. PMID: 16412396, PII: S0006-8993(05)01689-6, DOI: 10.1016/j.brainres.2005.11.078, ISSN: 0006-8993.

Zhang DQ, Zhou T, Ruan GX, McMahon DG. Circadian rhythm of Period1 clock gene expression in NOS amacrine cells of the mouse retina. Brain Res. 2005 Jul 7/19/2005; 1050(1-2): 101-9. PMID: 15978557, PII: S0006-8993(05)00780-8, DOI: 10.1016/j.brainres.2005.05.042, ISSN: 0006-8993.

Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A. Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Mar 3/1/2005; 102(9): 3495-500. PMID: 15728379, PMCID: PMC549289, PII: 0407737102, DOI: 10.1073/pnas.0407737102, ISSN: 0027-8424.

Ohta H, Yamazaki S, McMahon DG. Constant light desynchronizes mammalian clock neurons. Nat. Neurosci [print-electronic]. 2005 Mar; 8(3): 267-9. PMID: 15746913, PII: nn1395, DOI: 10.1038/nn1395, ISSN: 1097-6256.

Hastings MH, Reddy AB, McMahon DG, Maywood ES. Analysis of circadian mechanisms in the suprachiasmatic nucleus by transgenesis and biolistic transfection. Meth. Enzymol. 2005; 393: 579-92. PMID: 15817313, PII: S0076687905930309, DOI: 10.1016/S0076-6879(05)93030-9, ISSN: 1557-7988.

Schmidt, KF and McMahon, DG. Modulation der signalverarbeitung in der netzhaut (Modulation of signal processing in the retina). Spiegel der Forschung. 1998; 15: 91-6.

Lu C, McMahon DG. Modulation of hybrid bass retinal gap junctional channel gating by nitric oxide. J. Physiol. (Lond.). 1997 Mar 3/15/1997; 499 ( Pt 3): 689-99. PMID: 9130165, PMCID: PMC1159287, ISSN: 0022-3751.

McMahon DG, Barlow RB. Visual responses in teleosts. Electroretinograms, eye movements, and circadian rhythms. J. Gen. Physiol. 1992 Jul; 100(1): 155-69. PMID: 1512556, PMCID: PMC2229122, ISSN: 0022-1295.

McMahon DG, Knapp AG, Dowling JE. Horizontal cell gap junctions: single-channel conductance and modulation by dopamine. Proc. Natl. Acad. Sci. U.S.A. 1989 Oct; 86(19): 7639-43. PMID: 2477845, PMCID: PMC298122, ISSN: 0027-8424.

Block GD, McMahon DG, Wallace FS and Friesen WO.. Cellular analysis of the Bulla ocular circadian pacemaker system I: A model for retinal organization. J. Comp. Physiol. 1984; 155: 365-78.

McMahon, DG, Wallace, SF and Block, DG. Cellular analysis of the Bulla ocular circadian system II: Neuro-physiological basis of circadian rhythmicity. J. Comp. Physiol. 1984; 155: 379-85.

Block, GD and McMahon, DG. Cellular analysis of the Bulla ocular circadian pacemaker system III: Localization of the circadian pacemaker. J. Comp. Physiol. 1984; 155: 387-95.

Available Postdoctoral Position Details
Posted: 4/20/2010
Post-Doctoral Position in Retinal Neurobiology

NIH-funded post-doctoral position available immediately to study the cellular and molecular mechanisms of neural network adaptation in the retina. The project examines the mechanisms by which retinal circuits are reconfigured according to the prevailing illumination conditions through the action of modulatory retinal neurotransmitters such as dopamine and through synaptic feedback. The focus is on novel retinal circuits and molecules that mediate retinal dopamine neuron heterogeneity, regulation of retinal dopamine by light, and the contribution of connexin channels to feedback at the first visual synapse. Novel transgenic mouse and zebrafish models developed in our laboratory enable in situ electrophysiological recording from dopaminergic amacrine neurons (DA neurons), and manipulation of channel gene expression in adult zebrafish retina. The position requires a PhD or MD with previous training in neuroscience. Previous training in retinal electrophysiology or imaging is a plus, but not required.
Vanderbilt presents an exceptional environment for training in visual neuroscience in the form of the Vanderbilt Vision Research Center (http://vision-research.vanderbilt.edu/index.php) which administers NEI core and training grants in vision research. The VVRC provides a focus of activity and interaction that facilitates collaborations among investigators. The broader Vanderbilt neuroscience community is extensive with more than 300 investigators in more than 50 departments, centers and institutes offering an outstanding environment for in-depth training and research in neuroscience.
To apply for this position please send a letter of interest, curriculum vitae and names of three references to Douglas G. McMahon, PhD, Professor of Biological Sciences and Pharmacology, Vanderbilt University, Department of Biological Sciences, VU Station B, Box 35-1634, Nashville, TN 37235-1634 (douglas.g.mcmahon@vanderbilt.edu; http://sitemason.vanderbilt.edu/mcmahonlab).


Postdoctoral Position in Serotonin and Circadian Neurobiology

Postdoctoral position available to study functional modulation of raphe serotonergic neurons by genetic manipulation of the serotonin gene network and the brain’s biological clock. The project will employ electrophysiological analysis of genetically marked raphe neurons, as well as single cell RT-PCR and real-time gene expression imaging to examine the effects on serotonergic neuron function of mutations in the serotonin and circadian gene networks. The project is funded through the NIMH/Vanderbilt Silvio O. Conte Center for Neuroscience Research which brings together a highly interactive group of researchers focused on the serotonergic system of the brain. Vanderbilt provides an outstanding environment for neuroscience research through the Vanderbilt Brain Institute, Vanderbilt Kennedy Center and the Center for Molecular Neuroscience. Experience in visualized brain slice recording is preferred.
To apply for this position please send a letter of interest, curriculum vitae and names of three references to Douglas G. McMahon, PhD, Professor of Biological Sciences and Pharmacology, Vanderbilt University, Department of Biological Sciences, VU Station B, Box 35-1634, Nashville, TN 37235-1634 (douglas.g.mcmahon@vanderbilt.edu; http://sitemason.vanderbilt.edu/mcmahonlab).