Michelle S. Mazei-Robison, PhD
Assistant Professor, Physiology
Ph.D., 2005, Vanderbilt University
Psychiatric disorders now comprise a significant health and financial burden in the US, costing billions in lost production and wages. Two of the more prevalent psychiatric disorders, depression and addiction, affect millions of adults, and current therapeutic options offer limited relief. Despite the prevalence of these disorders, little is known about their underlying mechanisms. Part of the difficulty in studying the etiology of psychiatric diseases is the dearth of animal models for human disorders such as depression. Recent work has utilized a chronic social defeat model in mice that induces symptoms relevant to depression and posttraumatic stress disorder. Using this model, the importance of the mesocorticolimbic dopamine (DA) system has been revealed. This pathway consists of DA neurons in ventral tegmental area (VTA) that project to the nucleus accumbens and prefrontal cortex.
The Mazei-Robison lab is interested in understanding the molecular mechanisms that underlie changes in VTA DA neuron signaling, morphology, and activity induced in neuropsychiatric disorders such as depression and addiction. Despite evidence that dysregulation of the mesocorticolimbic DA system contributes to a number of psychiatric disorders, a detailed understanding of the main projection neurons in this pathway, the DA neurons of the VTA, is lacking. This includes the structural and functional neuroadaptations, the molecular mechanisms responsible for these adaptations, and the specific neurons and outputs affected. In particular, we are interested in the following questions:
- Which signaling pathways in the VTA are altered by stress and drugs to mediate changes in behavior?
- Are there morphological changes in VTA DA neurons that mediate long-term changes in behavior?
- Are all DA neurons in the VTA similarly affected or are changes specific for subtypes of neurons in the VTA or specific output pathways?
To address these aims, we employ a wide array of cutting-edge techniques including: a battery of behavioral assays including social interaction, elevated plus maze, and conditioned place preference; neuron- and projection-specific viral-mediated gene transfer and inducible- and brain region-specific transgenic mice; optogenetic control of neuronal activity during behavioral assays; retrograde labeling, cell-filling and 3D neuronal reconstruction; immunohistochemistry, and biochemical assays such as western blotting and quantitative real-time PCR.
Overall, these studies seek to identify and characterize the molecular underpinnings of stress- and drug-induced neuroadaptations in the mesocorticolimbic circuit with the goal of illuminating novel therapeutic targets.