Xiaoxi Zhuang
Associate Professor
Department of Neurobiology
The University of Chicago
947 E. 58th St., MC0926
Chicago, IL 60637
Email: xzhuang@bsd.uchicago.edu
Phone: (773) 834-9063
Office: Jules Knapp Research Building, Room 216
Research Summary
We investigate the molecular machinery for information processing in the basal ganglia (especially modulation by dopamine) that underlies reward learning, motivation, response selection and motor control. Our main approaches include mouse genetics, physiology, pharmacology and animal learning behavioral paradigms.
Research Description
We investigate the molecular machinery for information processing in the basal ganglia (especially modulation by dopamine) that underlies reward learning, motivation, response selection and motor control. Our main approaches include mouse genetics, physiology, pharmacology and animal learning behavioral paradigms.
The role of dopamine in reward and reward-dependent behavioral modification: Animal behaviors can be largely modified by reward/punishment history. Understanding the neurobiological basis of reward learning, motivation and response selection is a critical step in understanding many mental disorders such as addiction and depression as well as overeating in obesity, and in developing novel therapies. We are focusing on the role of tonic versus phasic dopamine, the corresponding postsynaptic signaling pathways and corticostriatal plasticity in the above processes.
As an extension of the above research, how do reward learning and motivation ultimately determine decision-making and choice behaviors? In a natural environment, these behaviors are critical for maximizing rewards/gains and minimizing risks/losses and for survival. We are investigating these more complex behaviors (e.g foraging) in a semi-natural environment and how genetic variations may affect fitness in this context.
The role of dopamine in motor learning and motor performance: In parallel to studies on the role of mesolimbic dopamine in reward learning and motivation, another focus of the lab is on the role of tonic versus phasic nigrostriatal dopamine, the corresponding postsynaptic signaling pathways and corticostriatal plasticity in motor learning and motor performance, in particular, in the context of Parkinson’s disease symptoms and therapies.
The biochemical basis of dopamine neuron degeneration in Parkinson's disease: Parkinson's disease is caused by progressive loss of dopamine neurons. Its biochemical basis is largely unknown. Both oxidative stress and dysfunction of the ubiquitin-proteasome pathway are implicated. We hypothesize that dopamine itself can cause oxidative stress. Under normal conditions, dopamine neurons are able to handle such cellular stress. However, in aged animals or in animals with genetic defects, dopamine neurons may die when protective mechanisms are impaired (e.g. defects in transporting dopamine to vesicles, defects in protein folding and protein degradation pathways). We are using in vivo transgenic mouse models as well as cell culture models to test this hypothesis.
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