Disruption of cerebellar microzonal organization in GluD2 (GluRδ2) knockout mouse.
Disruption of cerebellar microzonal organization in GluD2 (GluRδ2) knockout mouse.
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DOI：
10.3389/fncir.2013.00130
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发表时间：
2013
影响因子：
3.5
通讯作者：
Kano M
中科院分区：
文献类型：
--
作者：
Hashizume M;Miyazaki T;Sakimura K;Watanabe M;Kitamura K;Kano M
小脑皮质有一个由许多微区组成的复杂的喙尾组织。同一微区中的浦肯野细胞（PC）显示出由来自下橄榄（IO）神经元的攀爬纤维（CF）的兴奋性输入诱发的复杂锋电位（CS）的同步活动。同步CS活动被认为取决于IO神经元之间的电耦合和橄榄小脑投射的解剖组织。为了确定CF-PC布线如何有助于微区的形成，我们检测了谷氨酸受体δ2敲除（GluD 2 KO）小鼠中相邻PC之间的同步CS活动，其中丰富的过剩CF使异位神经支配到PC的远端树突上。我们进行了体内双光子钙成像PC人群检测CF输入。GluD 2基因敲除小鼠的相邻PC表现出比野生型（对照）小鼠更高的钙瞬变同步性。此外，在GluD 2 KO小鼠中，当PC之间的中外侧间隔达到~200 μm时，同步性几乎没有下降，这与对照小鼠中同步性的下降形成鲜明对比。增强的同步性仅部分受到间隙连接偶联阻断的影响。另一方面，GluD 2基因敲除小鼠的横向CF侧支延伸到微区边界之外，并在邻近PC的树突上形成局部聚集的异位突触。此外，在GluD 2基因敲除小鼠的PC表现出集群放电（Cf），特征CF反应，没有发现在野生型小鼠的PC。重要的是，Cf通常与PC远端树突中的局部钙瞬变相关，这可能有助于GluD 2 KO小鼠中钙信号的同步性增强。因此，我们的研究结果表明，CF信号在GluD 2基因敲除小鼠跨多个微区传播，并正确形成纵向橄榄小脑投影是必不可少的CS活动在小脑的时空组织。
Cerebellar cortex has an elaborate rostrocaudal organization comprised of numerous microzones. Purkinje cells (PCs) in the same microzone show synchronous activity of complex spikes (CSs) evoked by excitatory inputs from climbing fibers (CFs) that arise from neurons in the inferior olive (IO). The synchronous CS activity is considered to depend on electrical coupling among IO neurons and anatomical organization of the olivo-cerebellar projection. To determine how the CF–PC wiring contributes to the formation of microzone, we examined the synchronous CS activities between neighboring PCs in the glutamate receptor δ2 knockout (GluD2 KO) mouse in which exuberant surplus CFs make ectopic innervations onto distal dendrites of PCs. We performed in vivo two-photon calcium imaging for PC populations to detect CF inputs. Neighboring PCs in GluD2 KO mice showed higher synchrony of calcium transients than those in wild-type (control) mice. Moreover, the synchrony in GluD2 KO mice hardly declined with mediolateral separation between PCs up to ~200 μm, which was in marked contrast to the falloff of the synchrony in control mice. The enhanced synchrony was only partially affected by the blockade of gap junctional coupling. On the other hand, transverse CF collaterals in GluD2 KO mice extended beyond the border of microzone and formed locally clustered ectopic synapses onto dendrites of neighboring PCs. Furthermore, PCs in GluD2 KO mice exhibited clustered firing (Cf), the characteristic CF response that was not found in PCs of wild-type mice. Importantly, Cf was often associated with localized calcium transients in distal dendrites of PCs, which are likely to contribute to the enhanced synchrony of calcium signals in GluD2 KO mice. Thus, our results indicate that CF signals in GluD2 KO mice propagate across multiple microzones, and that proper formation of longitudinal olivo-cerebellar projection is essential for the spatiotemporal organization of CS activity in the cerebellum.
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影响因子：
2.5
作者：
HAWKES, R;LECLERC, N
通讯作者：
LECLERC, N
影响因子：
2.5
作者：
BROCHU, G;MALER, L;HAWKES, R
通讯作者：
HAWKES, R
影响因子：
5.3
作者：
Hashimoto, K;Ichikawa, R;Kano, M
通讯作者：
Kano, M
影响因子：
5.3
作者：
Blenkinsop, TA;Lang, EJ
通讯作者：
Lang, EJ
影响因子：
2.9
作者：
Hashimoto, K;Kano, M
通讯作者：
Kano, M