Behavioral Neuroscience Program, Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA.
Neurosci Biobehav Rev. 2018 Sep;92:67-82. doi: 10.1016/j.neubiorev.2018.05.021. Epub 2018 May 18.
Traditionally, dopamine (DA) and acetylcholine (ACh) striatal systems were considered antagonistic and imbalances or aberrant signaling between these neurotransmitter systems could be detrimental to basal ganglia activity and pursuant motor function, such as in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). Herein, we discuss the involvement of cholinergic interneurons (ChIs) in striatally-mediated movement in a healthy, parkinsonian, and dyskinetic state. ChIs integrate numerous neurotransmitter signals using intrinsic glutamate, serotonin, and DA receptors and convey the appropriate transmission onto nearby muscarinic and nicotinic ACh receptors to produce movement. In PD, severe DA depletion causes abnormal rises in ChI activity which promote striatal signaling to attenuate normal movement. When treating PD with L-DOPA, hyperkinetic side effects, or LID, develop due to increased striatal DA; however, the role of ChIs and ACh transmission, until recently has been unclear. Fortunately, new technology and pharmacological agents have facilitated understanding of ChI function and ACh signaling in the context of LID, thus offering new opportunities to modify existing and discover future therapeutic strategies in movement disorders.
传统上，多巴胺 (DA) 和乙酰胆碱 (ACh) 纹状体系统被认为是拮抗的，这些神经递质系统之间的不平衡或异常信号可能对基底神经节活动和随后的运动功能有害，如在帕金森病 (PD) 和左旋多巴诱导的运动障碍 (LID) 中。本文讨论了在健康、帕金森病和运动障碍状态下，胆碱能中间神经元 (ChIs) 在纹状体介导的运动中的作用。ChIs 使用内在的谷氨酸、血清素和 DA 受体整合众多神经递质信号，并将适当的信号传递到附近的毒蕈碱和烟碱 ACh 受体上，以产生运动。在 PD 中，严重的 DA 耗竭导致 ChI 活性异常升高，从而促进纹状体信号传递以减弱正常运动。当用 L-DOPA 治疗 PD 时，由于纹状体 DA 增加，会出现多动副作用或 LID；然而，直到最近，ChIs 和 ACh 传递的作用还不清楚。幸运的是，新技术和药理学试剂促进了对 LID 中 ChI 功能和 ACh 信号传递的理解，从而为修改现有治疗策略和发现运动障碍的新治疗策略提供了新的机会。
