Xiaoxi Zhuang PhD (Department of Neurobiology) is interested the role of the neurotransmitter, dopamine, in pathological behaviors and processes. He is investigating in how the specific aspects of reward are mediated by dopamine given its role in reinforcement learning and motivation that underlie addiction.
Using transgenic mice with altered dopaminergic activity, his group found that elevated dopaminergic tone enhanced motivation without altering reinforcement learning. They are now interested in testing whether the phasic dopaminergic activity mediates reinforcement learning by examining, using genetic manipulation, the signaling pathways in striatal neurons that differentially process tonic versus phasic dopamine signals.
In related work Dr. Zhuang is studying Parkinson’s disease, which is associated with the progressive, unexplained, loss of dopamine neurons. Because both oxidative stress, leading to protein misfolding, and dysfunction of the ubiquitin-proteasome pathway have been implicated. Zhuang’s group is investigating whether dopamine itself can cause oxidative stress and eventually dopamine neuron loss. They are testing whether loss or impairment of protective mechanisms (e.g. defects in transporting dopamine to vesicles, defects in protein folding and degradation pathways) prevent dopamine neurons from tolerating dopamine-mediated cellular stress that is not a problem under normal conditions, leading to dopaminergic cell loss. This is under investigation using in vivo transgenic mouse models.
These studies on addiction and on Parkinson’s disease will not only reveal molecular targets for therapeutic interventions, but will also provide valid animal models to test potential therapeutic agents or approaches.