Douglas G. McMahon is a professor of Biological Sciences and Pharmacology at

Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million ...

. McMahon has contributed several important discoveries to the field of

chronobiology Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobi ...

and vision. His research focuses on connecting the anatomical location in the brain to specific behaviors. As a graduate student under

Gene Block Gene David Block (born August 17, 1948) is an American biologist who has served as the current and 6th chancellor of the University of California, Los Angeles since August 2007. Block has served as provost and professor of biology at the Univer ...

, McMahon identified that the basal retinal neurons (BRNs) of the molluscan eye exhibited

circadian rhythms A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...

in spike frequency and membrane potential, indicating they are the clock neurons. He became the 1986 winner of the

Society for Neuroscience The Society for Neuroscience (SfN) is a professional society, headquartered in Washington, DC, for basic scientists and physicians around the world whose research is focused on the study of the brain and nervous system. It is especially well kn ...

's Donald B. Lindsley Prize in Behavioral Neuroscience for his work. Later, he moved on to investigate visual, circadian, and serotonergic mechanisms of

neuroplasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of Neural circuit, neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that diffe ...

. In addition, he helped find that constant light can desynchronize the circadian cells in the

suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regula ...

(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 Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene ''Opn4''. In the mammalian retina, there are two additional categories of opsins, both involved in the for ...

containing

ganglion cells {{stack, A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include: * Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina * Cells that reside in the adrenal medulla, where they are involved in the s ...

and the retinal dopaminergic amacrine neurons.

Biography

Education

McMahon earned his Bachelor of Arts in biology from

University of Virginia The University of Virginia (UVA) is a Public university#United States, public research university in Charlottesville, Virginia. Founded in 1819 by Thomas Jefferson, the university is ranked among the top academic institutions in the United S ...

in 1980. Immediately after graduating, McMahon began a Ph.D. program in biology at

Northwestern University Northwestern University is a private research university in Evanston, Illinois. Founded in 1851, Northwestern is the oldest chartered university in Illinois and is ranked among the most prestigious academic institutions in the world. Charte ...

. However, in 1981, McMahon found himself back at the University of Virginia where he completed his Ph.D. in biology under

Gene D. Block Gene David Block (born August 17, 1948) is an American biologist who has served as the current and 6th chancellor of the University of California, Los Angeles since August 2007. Block has served as Provost (education), provost and professor of b ...

. 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 Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

with John E. Dowling.

Scientific achievements

Neuronal circadian pacemakers

McMahon's work on molluscs with

led to a better understanding of the daily activity of the oscillating pacemaker cells. 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 An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, c ...

. The change in electrical activity manifests itself as a phase shift within the organism. Further research led them to find that phase shifting is a calcium-dependent process. They found that lowering extracellular levels of calcium actually prevents the organism from phase shifting in response to light without affecting the response of the neurons to light. 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. Basal Retinal Neuron

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 Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

that mediate transmission at electrical and

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/ aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...

synapses and the modulatory effects of dopamine and

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

on retinal synapse networks. Through studies with

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

he discovered that the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

decreases the electrical coupling within

horizontal cells Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, horizo ...

. Further research showed that it was the increase of

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

within the cell resulting from dopamine binding to

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...

that led to this decrease in coupling. McMahon and his colleagues also demonstrated that exogenous nitric oxide and

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

can modulate AMPA receptor mediated synaptic transmission at

gap junctions Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...

in hybrid bass retinal neurons.

Isolating the BRN

The work that won McMahon the Donald B. Lindsey Prize for PhD candidates involved locating and isolating specific regions of the eye that possessed circadian rhythms in '' Bulla gouldiana''. Under the mentorship of

, McMahon recorded from the basal retinal neurons (BRNs), a homogenous group of neurons that are 15-25μm in diameter, of the snail's eye and found that they could entrain to light/dark cycles, and even oscillate in constant darkness with a consistent intrinsic period. The BRN was later shown to entrain to light/dark cycles, and control physiological and behavioral oscillations within the entire organism. McMahon and Block found an increase in firing frequency and

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...

of the BRNs during the day, but the opposite at night. In addition, electrical activity between action potentials in the

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

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. Later work by Dr. Stephan Michel using a surgical

reductionist Reductionism is any of several related philosophical ideas regarding the associations between phenomena which can be described in terms of other simpler or more fundamental phenomena. It is also described as an intellectual and philosophical pos ...

approach provided further evidence that isolated BRNs were capable of circadian oscillations in their conductance.

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

containing

. McMahon's lab developed

mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

models, which enable in situ electrophysiological recording from DA neurons. In early 2015, McMahon and his graduate students, Jeff Jones and Michael Tackenberg, found that circadian rhythms in mice could be shifted by artificial stimulus to the

(SCN) using a laser and optical fiber. Using

optogenetics Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individu ...

, 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 Seasonal affective disorder (SAD) is a mood disorder subset, in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year. Common symptoms include sleeping too much, having li ...

, reduce the adverse health effects of working a night shift, and even alleviate the symptoms of

jet lag Jet lag is a physiological condition that results from alterations to the body's circadian rhythms caused by rapid long-distance trans-meridian (east–west or west–east) travel. For example, someone flying from New York to London, i.e. fr ...

. In 2014, McMahon, along with Chad Jackson, Megan Capozzi, and Heng Dai, found that mice exposed to short, winter-like, light cycles showed enduring deficits in photopic retinal light responses and visual contrast sensitivity. Additionally, dopamine levels were significantly lower in short photoperiod mice. These findings suggest that seasonal light cycles experienced during retinal development and maturation have lasting influences on retinal and visual function, likely through developmental programming of retinal dopamine.

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,

* 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 The University of Kentucky (UK, UKY, or U of K) is a Public University, public Land-grant University, land-grant research university in Lexington, Kentucky. Founded in 1865 by John Bryan Bowman as the Agricultural and Mechanical College of Kentu ...

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,

Positions

McMahon has held multiple positions in academia: * 1981-1986: Research Assistant, Department of Biology,

* 1986-1990: Postdoctoral Fellow, Dept. of Cellular and Developmental Biology,

* 1987: Grass Fellow, Marine Biological Laboratory, Woods Hole, MA. * 1990-1996: Assistant Professor, Department of Physiology,

* 1996-2001: Associate Professor, Department of Physiology, University of Kentucky * 2001-2002: Director, University of Kentucky

NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

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,

* 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 Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...

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

References

External links

Society for Research on Biological Rhythms
{{DEFAULTSORT:McMahon, Douglas G. Vanderbilt University faculty Living people Australian pharmacologists University of Virginia alumni Chronobiologists Northwestern University alumni Year of birth missing (living people) 21st-century American biologists