I am interested in the mechanisms by which neural circuits in the basal ganglia and their input structures produce volitional, motivated behavior. In particular, I aim to elucidate the function of neuronal cell types that are implicated in voluntary movement, especially maladaptive actions such as compulsive behavior. I am also interested in the genetic basis of individual trait differences that can predispose individuals to maladaptive behaviors, and how they map onto specific cell types in the brain.
As a PhD student, I combined molecular genetic and behavioral techniques to elucidate the role of striatal neurotransmitter receptors in response inhibition and motor skill learning. Most prominently, I characterized a D2 dopamine receptor knockdown mouse line and tested the sufficiency of virally restoring D2 receptor expression in the anterior dorsolateral striatum for rescuing behaviors that are impaired in these mice.
My postdoctoral research is inspired by the influential hypothesis that nucleus accumbens can influence dopamine release in associative and sensorimotor domains of the striatum through striato-nigro-striatal loops that “spiral” in a ventromedial to dorsolateral direction. Although anatomical evidence is significant, there is a paucity of functional evidence to substantiate the hypothesis. I am generating such evidence using a combination of voltammetry and optogenetics. As part of this project, I am also examining the role of topographical projections to the basal ganglia from hindbrain cholinergic and glutamatergic nuclei in controlling dopamine release in different functional subunits of the striatum, and their interactions with striatonigral inputs to the ventral midbrain. Furthermore, I elucidate how behavioral experience and/or drug exposure can alter the balance between these inputs. To complement my functional circuit mapping studies, I anatomically trace the topography of striatal output projections and the nigrostriatal projection with viral approaches.
Ever since I was young, I have been drawn to science, which led me to join the science team of my high school. Qualifying for, placing highly in, and winning competitions at the regional and national level inspired pursuit of a science major as a Bachelor’s student at Stanford University. I originally wanted to be a chemist like my parents, so I spent almost a year in Jim Collman’s laboratory in the Department of Chemistry synthesizing and testing porphyrin catalysts for chiral oxygenation of cyclic alkanes. Eventually I realized non-biological chemistry is not my intellectual passion, so my burgeoning interest in neurochemistry led me to switch to neurobiology. At the end of my junior year, I joined Robert Malenka’s laboratory in the Department of Psychiatry to conduct my thesis research for departmental honors in Biological Sciences. The incredibly intellectually stimulating environment of his laboratory kindled a desire within me to pursue a PhD in neuroscience. After successfully completing my honors thesis, I did a yearlong stint as a technician in the laboratory of John Huguenard. I then moved to another technician position in David Sulzer’s laboratory at Columbia University Medical Center, returning to dopamine and the basal ganglia, and I have stayed in the field ever since. In 2007, I was the first graduate student to enroll in the joint PhD program of Janelia Research Campus and the University of Chicago, conducting research in the laboratories of Alla Karpova and Xiaoxi Zhuang. I received my PhD in 2014 for research in the Zhuang laboratory, and began my current position in 2015.