Day Michelle, Wang Zhongfeng, Ding Jun, An Xinhai, Ingham Cali A, Shering Andrew F, Wokosin David, Ilijic Ema, Sun Zhuoxin, Sampson Allan R, Mugnaini Enrico, Deutch Ariel Y, Sesack Susan R, Arbuthnott Gordon W, Surmeier D James
Department of Physiology, 303 East Chicago Avenue, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Nat Neurosci. 2006 Feb;9(2):251-9. doi: 10.1038/nn1632. Epub 2006 Jan 15.
Parkinson disease is a common neurodegenerative disorder that leads to difficulty in effectively translating thought into action. Although it is known that dopaminergic neurons that innervate the striatum die in Parkinson disease, it is not clear how this loss leads to symptoms. Recent work has implicated striatopallidal medium spiny neurons (MSNs) in this process, but how and precisely why these neurons change is not clear. Using multiphoton imaging, we show that dopamine depletion leads to a rapid and profound loss of spines and glutamatergic synapses on striatopallidal MSNs but not on neighboring striatonigral MSNs. This loss of connectivity is triggered by a new mechanism-dysregulation of intraspine Cav1.3 L-type Ca(2+) channels. The disconnection of striatopallidal neurons from motor command structures is likely to be a key step in the emergence of pathological activity that is responsible for symptoms in Parkinson disease.
帕金森病是一种常见的神经退行性疾病，会导致难以有效地将想法转化为行动。虽然已知支配纹状体的多巴胺能神经元在帕金森病中会死亡，但尚不清楚这种损失是如何导致症状的。最近的研究表明纹状体苍白球中型多棘神经元（MSNs）参与了这一过程，但这些神经元如何以及确切为何发生变化尚不清楚。利用多光子成像技术，我们发现多巴胺耗竭会导致纹状体苍白球MSNs上的棘突和谷氨酸能突触迅速而显著地丧失，但邻近的纹状体黑质MSNs则不会。这种连接性的丧失是由一种新机制——棘突内Cav1.3 L型钙通道失调引发的。纹状体苍白球神经元与运动指令结构的断开连接可能是导致帕金森病症状的病理活动出现的关键步骤。
