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Department of Pharmacology

Douglas McMahon, Ph.D.

Professor of Biological Sciences
Stevenson Chair in Biological Sciences

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,

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.

Selected Publications