Divergent pallidal pathways underlying distinct Parkinsonian behavioral deficits.

Divergent pallidal pathways underlying distinct Parkinsonian behavioral deficits.
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DOI:
10.1038/s41593-021-00810-y
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发表时间:
2021-04
影响因子:
25
通讯作者:
Lim BK
Lim BK
中科院分区:
医学1区
文献类型:
--
作者:
Lilascharoen V;Wang EH;Do N;Pate SC;Tran AN;Yoon CD;Choi JH;Wang XY;Pribiag H;Park YG;Chung K;Lim BK

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基底神经节调节广泛的行为,包括运动控制和认知功能,并在帕金森病(PD)中受到深刻影响。然而,不同的基底神经节核团的功能组织尚未完全阐明在电路水平。在这项研究中,我们研究了不同的小白蛋白表达的神经元群体在外部苍白球(GPe-PV)的功能作用,以及它们对不同的PD相关行为的贡献。我们证明,黑质网状部(SNr)投射GPe-PV神经元和丘脑旁束(PF)投射GPe-PV神经元与运动和逆转学习,分别。在PD小鼠模型中,我们发现选择性操纵SNr投射GPe-PV神经元减轻了运动缺陷,而操纵PF投射GPe-PV神经元则挽救了受损的逆转学习。我们的研究结果建立了两个不同的GPe-PV神经元群体的行为的重要性,从而提供了一个新的框架,了解不同的行为缺陷的电路基础在帕金森病状态。
The basal ganglia regulate a wide range of behaviors, including motor control and cognitive functions, and are profoundly affected in Parkinson’s disease (PD). However, the functional organization of different basal ganglia nuclei has not been fully elucidated at the circuit level. In this study, we investigated the functional roles of distinct parvalbumin-expressing neuronal populations in the external globus pallidus (GPe-PV) and their contributions to different PD-related behaviors. We demonstrate that substantia nigra pars reticulata (SNr)-projecting GPe-PV neurons and parafascicular thalamus (PF)-projecting GPe-PV neurons are associated with locomotion and reversal learning, respectively. In a mouse model of PD, we found that selective manipulation of the SNr-projecting GPe-PV neurons alleviated locomotor deficit, whereas manipulation of the PF-projecting GPe-PV neurons rescued the impaired reversal learning. Our findings establish the behavioral importance of two distinct GPe-PV neuronal populations and, thereby, provide a new framework for understanding the circuit basis of different behavioral deficits in the Parkinsonian state.
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