IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice.
IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice.
复制标题
小脑/脑干中的 IP3R1 缺陷通过触发小鼠的强直性浦肯野细胞放电而导致基底神经节独立的肌张力障碍。
DOI：
10.3389/fncir.2013.00156
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发表时间：
2013
影响因子：
3.5
通讯作者：
Mikoshiba K
中科院分区：
文献类型：
--
作者：
Hisatsune C;Miyamoto H;Hirono M;Yamaguchi N;Sugawara T;Ogawa N;Ebisui E;Ohshima T;Yamada M;Hensch TK;Hattori M;Mikoshiba K
1 型肌醇 1,4,5-三磷酸受体 (IP3R1) 是内质网上的 Ca2+ 通道，是三种 IP3R 中大脑中的主要亚型。缺乏 IP3R1 的小鼠表现出癫痫样行为；然而，IP3R1 缺失导致异常运动的细胞和神经回路机制尚不清楚。在这里，我们发现小脑和脑干中专门缺乏 IP3R1 的条件性基因敲除小鼠会出现肌张力障碍，并表明小脑浦肯野细胞 (PC) 放电模式与特定的肌张力障碍运动相关。对自由行为小鼠的记录揭示了分别与身体伸展和僵硬相关的低频和高频 PC 复合物尖峰的时期。值得注意的是，肌张力障碍症状与基底神经节无关，可以通过小脑、下橄榄失活或在缺乏 PC 的情况下得到缓解。这些发现暗示小脑中 IP3R1 依赖性 PC 放电模式在运动协调中的作用以及通过橄榄小脑通路表达肌张力障碍。
The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca2+ channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking IP3R1 specifically in the cerebellum and brainstem experience dystonia and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific dystonic movements. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate IP3R1-dependent PC firing patterns in cerebellum in motor coordination and the expression of dystonia through the olivo-cerebellar pathway.
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影响因子：
3.5
作者：
Gardner, RJM;Knight, MA;Storey, E
通讯作者：
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3.5
作者：
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通讯作者：
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