Jun Wang, PhD

Education and Training

• Tongji Medical University, MD
• Shanghai Brain Research Institute, Chinese Academy of Sciences, PhD
• University of California at Berkeley and at San Francisco, Postdoctoral Fellow

Research Interests

• The Wang lab's research focuses on the role of basal ganglia circuitry in the neurobiological basis of neuropsychiatric diseases. These diseases include alcohol use disorder (alcohol addiction), opioid use disorder, and Alzheimer's disease.
• The dorsal striatum of the basal ganglia circuitry. The dorsal striatum, a main entry of the basal ganglia, is divided into the dorsomedial (DMS) and dorsolateral (DLS) striatum. The DMS mediates goal-directed behaviors, whereas the DLS controls habit learning. The DMS receives excitatory inputs from the cortex (e.g., the medial prefrontal cortex) and thalamus (e.g., the parafascicular nucleus or PfN). The striatum contains principal medium spiny neurons (MSNs) and cholinergic interneurons (CINs). Dopamine D1 receptor-expressing MSNs (D1R-MSNs or dMSNs) project to the substantia nigra pars reticulata (SNr) and entopeduncular nucleus (EP), giving rise to the direct pathway. D2R-expressing MSNs (D2R-MSNs or iMSNs) project to the internal globus pallidus (GPe), which, in turn, innervates the SNr and EP, forming the indirect pathway.
• Synaptic plasticity and alcohol use disorder. The Wang lab is interested in exploring alcohol-induced input (the mPFC versus thalamus)- and cell type (dMSNs versus iMSNs)-specific plasticity in the DMS. Using a combination of slice electrophysiology, optogenetics, viral and animal transgenics, and FosTRAP/ArcTRAP approaches, the Wang group investigates how alcohol self-administration causes synapse-specific aberrant plasticity in DMS neuronal ensembles and how these synaptic alterations are involved in pathological drinking. In addition, the few available medications for alcoholism often fail to prevent relapse to alcohol, perhaps because they do not reverse the alcohol-evoked long-term synaptic plasticity, which likely drives alcohol seeking and relapse. The Wang lab employs dual-channel optogenetics to normalize the alcohol-induced circuit-specific plasticity, thereby persistently reducing alcohol seeking and relapse in operant self-administration. They express two excitatory rhodopsins, Chrons and Chrimson, in the presynaptic terminals and postsynaptic MSNs and activate them using blue and yellow light, respectively. They then induce long-term potentiation (LTP) or depression (LTD) in vivo using optogenetic high-frequency stimulation (HFS) or spike-timing-dependent protocols (STDP) to change animal-seeking and relapsing behavior persistently.
• Cognitive flexibility and alcohol use disorder. The Wang lab is also interested in elucidating the mechanism of compulsive inflexible drinking. They study how pathological drinking alters thalamic PfN-->CIN activity in reversal learning of instrumental action-outcome contingency and how the drinking alters CIN-mediated regulation of corticostriatal transmission in dMSNs and iMSNs. The results of the alcohol research will guide future efforts toward the development of more effective therapeutics for alcohol use disorders. * Striatal patch versus matrix compartments and opioid use disorder. The striatal patch (striosome) compartment contains extensive mu-opioid receptors (MORs). The Wang lab investigates how MOR-expressing MSNs, the non-motor outputs of the basal ganglia (i.e., EP), and their downstream circuit (i.e., the lateral habenula), contribute to opioid use disorder, with a particular interest in fentanyl abuse.
• Alzheimer's disease and striatal dysfunction. Human MRI studies found Aβ deficits in the striatum of Alzheimer's patients who showed motor-related deficits. The Wang lab explores how corticostriatal transmission in MSNs, CIN activity, and cholinergic neuron activity in the basal forebrain are altered in the 5xFAD mouse model of Alzheimer's disease. They are also interested in how alcohol drinking exacerbates these alterations.
• Dr. Wang participates in graduate training as a faculty member in the Medical Science Ph.D. program in the College of Medicine, the Interdisciplinary Program in Neuroscience (TAMIN), and the Interdisciplinary Toxicology Program.