Functional Coupling between mGluR1 and Cav3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines
Functional Coupling between mGluR1 and Cav3.1 T-Type Calcium Channels Contributes to Parallel Fiber-Induced Fast Calcium Signaling within Purkinje Cell Dendritic Spines
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DOI：
10.1523/jneurosci.0362-09.2009
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发表时间：
2009-08-05
影响因子：
5.3
通讯作者：
Snutch, Terrance P.
中科院分区：
文献类型：
--
作者：
Hildebrand, Michael E.;Isope, Philippe;Snutch, Terrance P.
T型电压门控钙通道在许多神经元的树突中表达，尽管它们与突触后受体的功能相互作用和对突触信号传导的贡献还不清楚。我们结合联合收割机电生理和超快双光子钙成像证实mGluR1激活通过G蛋白和酪氨酸磷酸酶依赖性途径增强小脑浦肯野细胞Ca（v）3.1 T型电流。对野生型和Ca（v）3.1基因敲除动物的免疫组织化学和电子显微镜研究表明，Ca（v）3.1 T型通道优先在浦肯野细胞树突棘中表达，并与mGluR1s共定位。我们进一步证明，平行纤维刺激诱导快速阈下钙信号在树突棘和突触Ca（v）3.1介导的钙瞬变增强mGluR1选择性地在突发的兴奋性平行纤维输入。我们的数据确定了一个新的快速钙信号通路在浦肯野细胞树突棘触发短脉冲的平行纤维输入和介导的T型钙通道和mGluR1。
T-type voltage-gated calcium channels are expressed in the dendrites of many neurons, although their functional interactions with postsynaptic receptors and contributions to synaptic signaling are not well understood. We combine electrophysiological and ultrafast two-photon calcium imaging to demonstrate that mGluR1 activation potentiates cerebellar Purkinje cell Ca(v)3.1 T-type currents via a G-protein-and tyrosine-phosphatase-dependent pathway. Immunohistochemical and electron microscopic investigations on wild-type and Ca(v)3.1 gene knock-out animals show that Ca(v)3.1 T-type channels are preferentially expressed in Purkinje cell dendritic spines and colocalize with mGluR1s. We further demonstrate that parallel fiber stimulation induces fast subthreshold calcium signaling in dendritic spines and that the synaptic Ca(v)3.1-mediated calcium transients are potentiated by mGluR1 selectively during bursts of excitatory parallel fiber inputs. Our data identify a new fast calcium signaling pathway in Purkinje cell dendritic spines triggered by short burst of parallel fiber inputs and mediated by T-type calcium channels and mGluR1s.