Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models
Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models
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DOI：
10.1038/nn1632
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发表时间：
2006-02-01
影响因子：
25
通讯作者：
Surmeier, DJ
中科院分区：
文献类型：
--
作者：
Day, M;Wang, ZF;Surmeier, DJ
帕金森病是一种常见的神经退行性疾病，导致难以有效地将思想转化为行动。虽然已知支配纹状体的多巴胺能神经元在帕金森病中死亡，但尚不清楚这种损失如何导致症状。最近的研究表明，纹状体中棘神经元（MSN）参与了这一过程，但这些神经元如何以及为什么会发生变化尚不清楚。使用多光子成像，我们表明，多巴胺耗竭导致的striatopallidal MSNs，但不是在邻近的striatonigral MSNs的棘和神经元突触的快速和深刻的损失。这种连通性的丧失是由一种新的机制触发的，即脊髓内Cav1.3 L型Ca2+通道的失调。纹状体苍白球神经元与运动指令结构的断开可能是导致帕金森病症状的病理活动出现的关键步骤。
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 Ca2+ 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.