Douglas G. McMahon

Douglas G. McMahon is a professor of Biological Sciences and Pharmacology at Vanderbilt University. McMahon has contributed several important discoveries to the field of chronobiology and vision. His research focuses on connecting the anatomical location in the brain to specific behaviors. As a graduate student under Gene Block, McMahon identified that the basal retinal neurons (BRNs) of the molluscan eye exhibited circadian rhythms in spike frequency and membrane potential, indicating they are the clock neurons. He became the 1986 winner of the Society for Neuroscience's Donald B. Lindsley Prize in Behavioral Neuroscience for his work. Later, he moved on to investigate visual, circadian, and serotonergic mechanisms of neuroplasticity. In addition, he helped find that constant light can desynchronize the circadian cells in the suprachiasmatic nucleus (SCN). He has always been interested in the underlying causes of behavior and examining the long term changes in behavior and physiology in the neurological modular system. McMahon helped identifying a retrograde neurotransmission system in the retina involving the melanopsin containing ganglion cells and the retinal dopaminergic amacrine neurons.

Biography

Education McMahon earned his Bachelor of Arts in biology from University of Virginia in 1980. Immediately after graduating, McMahon began a Ph.D. program in biology at Northwestern University. However, in 1981, McMahon found himself back at the University of Virginia where he completed his Ph.D. in biology under Gene D. Block. It was during this time that McMahon discovered the basal retinal neurons of the molluscan eye were the clock neurons. From 1986-1990, McMahon conducted his post-doctoral work in neurobiology at Harvard University with John E. Dowling. Prior to this discovery, the identity of neuron types participating in retinal networks was largely known, but the specific physiological roles of the identified morphological structures were poorly understood. In 2011, McMahon and Block found that retinal neurons in molluscs were active during the day, but inactive at night. Electrical stimulation at the tissue level of the retinal neurons during the day did not affect the organism. However, electrical stimulation at night caused a phase shift in the organism. Because stimulation yielded a phase shift, the results suggested that the retina contained a biological clock. McMahon and Block devised a model explaining these phenomena: light during the day does not have much of an effect on the neurons' activity, as they are already active. Light at night, on the other hand, when these neurons are inactive, stimulates them and causes them to fire action potentials. The change in electrical activity manifests itself as a phase shift within the organism. Around the same time, while Block and McMahon were conducting this experiment, other scientists discovered how to clone the period gene, marking an exciting time in the young field of chronobiology.thumb

Retinal research McMahon contributed to the understanding of retinal neurophysiology alongside his post-doctoral mentor, John E. Dowling. His early research focused on ion channels that mediate transmission at electrical and glutamatergic synapses and the modulatory effects of dopamine and nitric oxide on retinal synapse networks. Through studies with zebrafish he discovered that the neurotransmitter dopamine decreases the electrical coupling within horizontal cells. Further research showed that it was the increase of cAMP within the cell resulting from dopamine binding to AMPA receptor that led to this decrease in coupling. The BRN was later shown to entrain to light/dark cycles, and control physiological and behavioral oscillations within the entire organism. In addition, electrical activity between action potentials in the optic nerve and the firing of the BRNs were shown to share a 1:1 correlation. In 1984, McMahon also demonstrated that the surgical removal of the photoreceptor layer failed to disrupt circadian rhythm in the Bulla eye, while the removal of the BRNs abolished circadian rhythm. His discovery that a fragment of Bulla retina containing as few as six intact BRN somata were sufficient for circadian rhythmogenesis further supported the BRNs as circadian pacemakers.

Recent research McMahon's lab is currently interested in three areas of research: the role of dopamine on visual function and retinal physiology, links between molecular, intracellular, electrical, and behavioral rhythms in the brain's biological clock, and how perinatal photoperiod affects the serotonergic system and anxious/depressive behavior. Alongside Dao-Qi Zhang, the lab has made significant contributions to the understanding of retinal neural network adaptation by dopaminergic amacrine neurons (DA neurons), revealing a retrograde neurotransmission pathway in the retina specifically involving melanopsin containing ganglion cells. McMahon's lab developed mouse models, which enable in situ electrophysiological recording from DA neurons. Using optogenetics, the Vanderbilt researchers were able to change the firing rate of neurons in the SCN so that their firing resembled their normal day and night activity levels. Subsequently, altering the firing rate of the SCN neurons reset the biological clocks of the mice. Prior to this experiment, firing rate was thought to be strictly an output of the SCN. However, the results from this experiment suggest that firing rate is a more complex mechanism that is yet to be fully understood. Although not ready for direct human use, optogenetic stimulation techniques such as the one used by McMahon could potentially be used to treat seasonal affective disorder, reduce the adverse health effects of working a night shift, and even alleviate the symptoms of jet lag.

Procedural Contributions McMahon's lab generated transgenic Per1::GFP mice in which a degradable form of recombinant jellyfish GFP reporter is driven by the mouse Per1 gene promoter. mPer1‐driven GFP fluorescence intensity reports light‐induction and circadian rhythmicity in neural structures of the SCN. The Per1::GFP transgenic mouse allows for the simultaneous quantification of molecular clock state and the firing rate of SCN neurons. Thus, this circadian reporter transgene depicts gene expression dynamics of biological clock neurons, giving a new view of this brain function.

Honors and awards

1980: Bachelor of Arts Degree with Distinction, University of Virginia 1985: Gwathmey Fellowship, Society of Fellows, University of Virginia 1986: Andrew Fleming Award for Dissertation Research, Dept. of Biology, University of Virginia 1986: Donald B. Lindsley Prize in Behavioral Neuroscience, Society for Neuroscience 1996: University of Kentucky College of Medicine Research Award 2000: University of Kentucky University Research Professorship 2000: University of Kentucky Charles Wethington Research Scholar 2007: NIMH Silvio O. Conte Investigator 2008: Chancellor's Award for Research, Vanderbilt University

Positions McMahon has held multiple positions in academia:

1981-1986: Research Assistant, Department of Biology, University of Virginia 1986-1990: Postdoctoral Fellow, Dept. of Cellular and Developmental Biology, Harvard University 1987: Grass Fellow, Marine Biological Laboratory, Woods Hole, MA. 1990-1996: Assistant Professor, Department of Physiology, University of Kentucky 1996-2001: Associate Professor, Department of Physiology, University of Kentucky 2001-2002: Director, University of Kentucky NIH Institutional Training Grant, "Cellular and Molecular Neuroscience of Sensory Systems" 2001 -2002: Donald T. Frazier Professor, Department of Physiology, University of Kentucky 2002–present: Professor, Department of Biological Sciences, Vanderbilt University 2005-2008: Director of Graduate Studies, Department of Biological Sciences, Vanderbilt University 2008–present: Professor, Department of Pharmacology, Vanderbilt University 2009–2014: Director of Graduate Studies, Neuroscience Program, Vanderbilt University Medical Center 2011-2014: Associate Director for Education and Training, Vanderbilt Brain Institute 2014–present: Stevenson Professor of Biological Sciences, Vanderbilt University 2014–present: Chair of the Department of Biological Sciences at Vanderbilt

Affiliations

McMahon has also been a member of many scientific communities. The most recent are listed below.

2000-2002: Chair, NIH Integrative Functional and Cellular Neuroscience 3 Study Section 2004-2007: AD HOC Reviewer, NIH BDPE Study Section 2007: Chair, IFCN-C Special Emphasis Panel, NIH 2008: AD HOC Reviewer, NIH ICP1 Study Section 2011: AD HOC Reviewer, NIH BDPE Study Section 2012: NIMH RDoC Consultant 2012: Ad Hoc Reviewer, NIH NPDR Study Section 2012: Ad Hoc Reviewer, NIH F02B Fellowship Review Panel