Department of Medical Neurobiology (Physiology), Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
The Edmond and Lily Safra Center (ELSC) for Brain Sciences, The Hebrew University, Jerusalem, Israel.
Mov Disord. 2015 Jul;30(8):1014-25. doi: 10.1002/mds.26300. Epub 2015 Jun 22.
Basal ganglia disorders such as Parkinson's disease, dystonia, and Huntington's disease are characterized by a dysregulation of the basal ganglia neuromodulators (dopamine, acetylcholine, and others), which impacts cortico-striatal transmission. Basal ganglia disorders are often associated with an imbalance between the midbrain dopaminergic and striatal cholinergic systems. In contrast to the extensive research and literature on the consequences of a malfunction of midbrain dopaminergic signaling on the plasticity of the cortico-striatal synapse, very little is known about the role of striatal cholinergic interneurons in normal and pathological control of cortico-striatal transmission. In this review, we address the functional role of striatal cholinergic interneurons, also known as tonically active neurons and attempt to understand how the alteration of their functional properties in basal ganglia disorders leads to abnormal cortico-striatal synaptic plasticity. Specifically, we suggest that striatal cholinergic interneurons provide a permissive signal, which enables long-term changes in the efficacy of the cortico-striatal synapse. We further discuss how modifications in the striatal cholinergic activity pattern alter or prohibit plastic changes of the cortico-striatal synapse. Long-term cortico-striatal synaptic plasticity is the cellular substrate of procedural learning and adaptive control behavior. Hence, abnormal changes in this plasticity may underlie the inability of patients with basal ganglia disorders to adjust their behavior to situational demands. Normalization of the cholinergic modulation of cortico-striatal synaptic plasticity may be considered as a critical feature in future treatments of basal ganglia disorders.
基底神经节疾病，如帕金森病、肌张力障碍和亨廷顿病，其特征是基底神经节神经调质（多巴胺、乙酰胆碱等）的失调，这会影响皮质纹状体的传递。基底神经节疾病通常与中脑多巴胺能和纹状体内胆碱能系统之间的不平衡有关。与广泛研究和文献相比，中脑多巴胺能信号转导功能障碍对皮质纹状体突触可塑性的影响，关于纹状体内胆碱能中间神经元在正常和病理性控制皮质纹状体传递中的作用知之甚少。在这篇综述中，我们探讨了纹状体内胆碱能中间神经元（也称为持续活跃神经元）的功能作用，并试图了解基底神经节疾病中其功能特性的改变如何导致皮质纹状体突触可塑性的异常。具体来说，我们认为纹状体内胆碱能中间神经元提供了一种许可信号，使皮质纹状体突触的效能发生长期变化。我们进一步讨论了纹状体内胆碱能活性模式的改变如何改变或阻止皮质纹状体突触的可塑性变化。长期皮质纹状体突触可塑性是程序性学习和适应性控制行为的细胞基础。因此，这种可塑性的异常变化可能是基底神经节疾病患者无法根据情境需求调整行为的原因。皮质纹状体突触可塑性的胆碱能调节的正常化可能被认为是未来治疗基底神经节疾病的关键特征。
