Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.
Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.
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DOI：
10.1038/s41586-018-0090-6
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发表时间：
2018-05
期刊：
影响因子：
64.8
通讯作者：
Schnitzer MJ
中科院分区：
文献类型：
--
作者：
Parker JG;Marshall JD;Ahanonu B;Wu YW;Kim TH;Grewe BF;Zhang Y;Li JZ;Ding JB;Ehlers MD;Schnitzer MJ
帕金森病中多巴胺的丢失被认为是通过在基底节的直接(DSPN)和间接(ISPN)通路中分别诱导纹状体棘投射神经元(SPN)活动减少和过度活动而阻碍运动。相反的失衡可能是过度运动异常的基础，例如用多巴胺前体L-多巴治疗帕金森病引起的运动障碍。在这里，我们监测了表现良好的小鼠在多巴胺耗竭前后以及L-多巴诱发的运动障碍期间数以千计的SPN。正常情况下，dSPN和iSPN的混合簇在运动前共同激活。多巴胺耗竭使SPN活动率失衡，并扰乱了编码运动的iSPN簇。与临床疗效相匹配，L多巴或D2多巴胺受体激动剂比D1多巴胺受体激动剂更有效地逆转这些异常。在L-多巴诱发的运动障碍中，iSPN表现为低活动，dSPN表现为无簇状的高活动，出现相反的病理生理过程。因此，SPN活动的时空分布和比率似乎对纹状体功能至关重要，下一代治疗基底节疾病应该针对纹状体活动的这两个方面。
Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson’s disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L -DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, L-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in L-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.
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通过基础神经节电路的光遗传控制对帕金森运动行为的调节。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Cui, Guohong;Jun, Sang Beom;Jin, Xin;Pham, Michael D.;Vogel, Steven S.;Lovinger, David M.;Costa, Rui M.
通讯作者：
Costa, Rui M.
影响因子：
25
作者：
Lecoq J;Savall J;Vučinić D;Grewe BF;Kim H;Li JZ;Kitch LJ;Schnitzer MJ
通讯作者：
Schnitzer MJ
影响因子：
--
作者：
Cenci, M. Angela;Konradi, Christine
通讯作者：
Konradi, Christine
影响因子：
16.2
作者：
Klaus A;Martins GJ;Paixao VB;Zhou P;Paninski L;Costa RM
通讯作者：
Costa RM