Overview: Vision, Rhythms, and Blues

 

Broadly stated, our lab is interested in understanding how the brain works.  Of course, the answer to that broad question can take many forms and encompass many facets of neuroscience, but the aspect of brain function which we find most compelling is 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, which take place in the brain when we adapt to new levels of stimuli, when we express daily biological rhythms, or when we learn.

 

These mechanisms mediate many basic mechanisms of the mind, regulating sensation, motivation, mood and sleep.  They prepare your eyes to face the light of dawn each day (through action on retinal circuits), initiate the motor movements to get you out of bed (in the brain's basal ganglia), register the first sip of coffee (in the reward circuitry), elevate your mood as you and the day get brighter, and, finally, send you off to sleep at night (through the brain's daily biological clock).

 

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 plasticity 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 inter-neuronal 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 major depression and bipolar disorders; and ocular disorders, such as photoreceptor degeneration and myopia.

 

Research Interests

Vision

 

How does the neurotransmitter dopamine modulate visual function and retinal physiology?

 

 

Multielectrode array recording

Electroretinography

Optokinetic tracking

Rhythms

 

What are the links between the molecular, intracellular, electrical, and behavioral rhythms in the brain's biological clock?

 

In vivo and ex vivo optogenetics

Real-time gene expression imaging

Electrophysiology

Blues

 

How does perinatal photoperiod affect the serotinergic system and anxious/depressive behavior?

 

 

Multielectrode array recording

Neurochemistry

Mouse behavior

 

Publications

The following is a brief listing of our most recent publications.  For a full list of publications, please click here.

 

Vision

 

Jackson, C.R., Capozzi, M., Dai, H. & McMahon, D.G. Circadian perinatal photoperiod has enduring effects on retinal dopamine and visual function. J. Neurosci. 26, 4627-4633 (2014).

McMahon, D.G., Iuvone, P.M. & Tosini, G. Circadian organization of the mammalian retina: from gene regulation to physiology and diseases. Prog. Retin. Eye Res39, 58-76 (2014).

Zhang, D.Q., Belenky, M.A., Sollars, P.J., Pickard, G.E. & McMahon, D.G. Melanopsin mediates retrograde visual signaling in the retina. PLoS One7, e42647 (2012).

Jackson, C.R., Ruan, G.X., Aseem, F., Abey, J., Gamble, K., Stanwood, G., Palmiter, R.D., Iuvone, P.M. & McMahon, D.G. Retinal dopamine mediates multiple dimensions of light-adapted vision. J. Neurosci32, 9359-9368 (2012).

Ruan, G.X., Gamble, K.L., Risner, M.L., Young, L.A. & McMahon, D.G. Divergent roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillators. PLoS One7, e38985 (2012).

Sun, Z., Risner, M.L. van Asselt, J.B., Zhang, D.Q., Kamermans, M. & McMahon, D.G. Physiological and molecular characterization of connexin hemichannels in zebrafish retinal horizontal cells. J. Neurophysiol107, 2624-2632 (2012).

Klaassen, L.J., et al. Synaptic transmission from horizontal cells to cones is impaired by loss of connexin hemichannels. PLoS Biol9, e1001107 (2011).

Frazao, R., et al. Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors. Invest. Ophthalmol. Vis. Sci52, 3083-3088 (2011).

Sun, Z., Zhang, D.Q. & McMahon, D.G. Zinc modulation of hemi-gap-junction channel currents in retinal horizontal cells. J. Neurophysiol101, 1774-1780 (2009).

 

Rhythms

 

Jones, J.R., Tackenberg, M.C. & McMahon, D.G. Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior. Nat. Neurosci. (In press).

Kudo, T., Tahara, Y., Gamble, K.L, McMahon, D.G., Block, G.D. & Colwell, C.S. Vasoactive intestinal peptide produces long-lasting changes in neural activity in the suprachiasmatic nucleus. J. Neurophysiol110, 1097-1106 (2013).

Gamble, K.L, Kudo, T., Colwell, C.S. & McMahon, D.G. Gastrin-releasing peptide modulates fast delayed rectifier potassium current in Per1-expressing SCN neurons. J. Biol. Rhythms26, 99-106 (2011).

Ciarleglio, C.M., Axley, J.C., Strauss, B.R., Gamble, K.L & McMahon, D.G. Perinatal photoperiod imprints the circadian clock. Nat. Neurosci14, 25-27 (2011).

Gamble, K.L., et al. Shift work in nurses: contribution of phenotypes and genotypes to adaptation. PLoS One6, e18395 (2011).

Ciarlegio, C.M., Gamble, K.L., Axley, J.C., Strauss, B.R., Cohen, J.Y., Colwell, C.S. & McMahon, D.G. Population encoding by circadian clock neurons organizes circadian behavior. J. Neurosci. 29, 1670-1676 (2009).

 

Blues

 

Ciarleglio, C.M., Resuehr, H.E., Axley, J.C., Deneris, E.S. & McMahon, D.G. Pet-1 deficiency alters the circadian clock and its temporal organization of behavior. PLoS One. 9, e97412 (2014).

Veenstra-VanderWeele, J., et al. Autism gene varient causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior. Proc. Natl. Acad. Sci. USA109, 5469-5474 (2012).

Ciarleglio, C.M., Resuehr, H.E. & McMahon, D.G., Interactions of the serotonin and circadian systems: nature and nurture in rhythms and blues. Neuroscience197, 8-16 (2011).

Thompson, B.J., et al. Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter. Proc Natl. Acad. Sci USA108, 3785-3790 (2011).

 

Lab Members

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    Contact    

 

8270 MRB III
Vanderbilt University

465 21st Ave S

Nashville, TN, 37235

 

douglas.g.mcmahon@vanderbilt.edu

 

Tel: 615-936-3933

Fax: 615-343-6707

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