@article{TEXTUAL,
      recid = {5645},
      author = {Cheung, Timothy H. C. and Ding, Yunmin and Zhuang, Xiaoxi  and Kang, Un Jung},
      title = {Learning critically drives parkinsonian motor deficits  through imbalanced striatal pathway recruitment},
      journal = {PNAS},
      address = {2023-03-15},
      number = {TEXTUAL},
      abstract = {Dopamine (DA) loss in Parkinson’s disease (PD) causes  debilitating motor deficits. However, dopamine is also  widely linked to reward prediction and learning, and the  contribution of dopamine-dependent learning to movements  that are impaired in PD—which often do not lead to explicit  rewards—is unclear. Here, we used two distinct motor tasks  to dissociate dopamine’s acute motoric effects vs. its  long-lasting, learning-mediated effects. In  dopamine-depleted mice, motor task performance gradually  worsened with task exposure. Task experience was critical,  as mice that remained in the home cage during the same  period were relatively unimpaired when subsequently probed  on the task. Repeated dopamine replacement treatments  acutely rescued deficits and gradually induced long-term  rescue that persisted despite treatment withdrawal.  Surprisingly, both long-term rescue and parkinsonian  performance decline were task specific, implicating  dopamine-dependent learning. D1R activation potently  induced acute rescue that gradually consolidated into  long-term rescue. Conversely, reduced D2R activation  potently induced parkinsonian decline. In dopamine-depleted  mice, either D1R activation or D2R activation prevented  parkinsonian decline, and both restored balanced activation  of direct vs. indirect striatal pathways. These findings  suggest that reinforcement and maintenance of  movements—even movements not leading to explicit  rewards—are fundamental functions of dopamine and provide  potential mechanisms for the hitherto unexplained  “long-duration response” by dopaminergic therapies in PD.},
      url = {http://knowledge.uchicago.edu/record/5645},
}