Cell-specific pallidal intervention induces long-lasting motor recovery in dopamine-depleted mice.
Cell-specific pallidal intervention induces long-lasting motor recovery in dopamine-depleted mice.
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DOI：
10.1038/nn.4559
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发表时间：
2017-06
影响因子：
25
通讯作者：
Gittis AH
中科院分区：
文献类型：
--
作者：
Mastro KJ;Zitelli KT;Willard AM;Leblanc KH;Kravitz AV;Gittis AH
基底神经节内不同细胞类型的鉴定在我们理解基底神经节功能和神经系统疾病的治疗中起着关键作用。外苍白球（GPe）是基底神经节中运动抑制通路的关键贡献者，但其神经元异质性仍然是治疗干预的未开发资源。在这里，我们证明了分离GPe中两个神经元群体的活性的光遗传学干预-使PV-GPe神经元的活性高于Lhx 6-GPe神经元的活性-恢复多巴胺耗尽小鼠的运动，并在刺激后数小时内减弱基底神经节输出神经元的病理活性。这些结果确立了GPe中细胞特异性干预的效用，以靶向功能不同的通路，尽管持续缺乏多巴胺，但仍有可能诱导运动的持久恢复。
The identification of distinct cell-types within the basal ganglia has played a critical role in our understanding of basal ganglia function and the treatment of neurological disorders. The external globus pallidus (GPe) is a key contributor to motor suppressing pathways in the basal ganglia, yet its neuronal heterogeneity has remained an untapped resource for therapeutic interventions. Here, we demonstrate that optogenetic interventions that dissociate the activity of two neuronal populations in the GPe – elevating the activity of PV-GPe neurons over that of Lhx6-GPe neurons – restores movement in dopamine depleted mice and attenuates pathological activity of basal ganglia output neurons for hours beyond stimulation. These results establish the utility of cell-specific interventions in the GPe to target functionally distinct pathways, with the potential to induce long-lasting recovery of movement despite the continued absence of dopamine.
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影响因子：
5.3
作者：
Holgado, Alejo J. Nevado;Terry, John R.;Bogacz, Rafal
通讯作者：
Bogacz, Rafal
影响因子：
7.7
作者：
Chin, Gordon D.;Hutchison, William D.
通讯作者：
Hutchison, William D.
影响因子：
5.3
作者：
Gittis, Aryn H.;Berke, Joshua D.;Schmidt, Robert
通讯作者：
Schmidt, Robert
影响因子：
56.9
作者：
GERFEN, CR;ENGBER, TM;SIBLEY, DR
通讯作者：
SIBLEY, DR
影响因子：
3
作者：
Bugaysen J;Bar-Gad I;Korngreen A
通讯作者：
Korngreen A