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多巴胺耗竭以依赖于通路的方式损害纹状体中的双侧感觉处理。

Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner.

机构信息

Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.

Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.

出版信息

Neuron. 2017 May 17;94(4):855-865.e5. doi: 10.1016/j.neuron.2017.05.004.

Abstract

Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection. This laterality coding was lost in DA-depleted mice due to adaptive changes in the intrinsic and synaptic properties, mainly, of direct pathway MSNs. L-DOPA treatment restored laterality coding by increasing the separation between ipsilateral and contralateral responses. Our results show that DA depletion impairs bilateral tactile acuity in a pathway-dependent manner, thus providing unexpected insights into the network mechanisms underlying sensory deficits in PD. VIDEO ABSTRACT.

摘要

帕金森病(PD)是一种由多巴胺能神经支配丧失引起的运动障碍,尤其是向纹状体的丧失。PD 患者常表现出感觉障碍,但潜在的网络机制尚不清楚。在这里,我们研究了多巴胺(DA)耗竭如何影响小鼠纹状体的感觉处理。我们在体内全细胞记录过程中使用光穴器在线鉴定直接和间接通路投射神经元(MSNs)。在对照小鼠中,MSNs 用对侧比同侧胡须偏斜更大和更早的反应来编码感觉输入的侧性。由于直接通路 MSNs 的内在和突触特性的适应性变化,这种侧性编码在 DA 耗竭的小鼠中丢失。L-DOPA 治疗通过增加同侧和对侧反应之间的分离来恢复侧性编码。我们的结果表明,DA 耗竭以通路依赖性方式损害双侧触觉锐度,从而为 PD 中感觉缺陷的网络机制提供了意想不到的见解。视频摘要。

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