Type 1 Inositol Trisphosphate Receptor Regulates Cerebellar Circuits by Maintaining the Spine Morphology of Purkinje Cells in Adult Mice
Type 1 Inositol Trisphosphate Receptor Regulates Cerebellar Circuits by Maintaining the Spine Morphology of Purkinje Cells in Adult Mice
复制标题
DOI：
10.1523/jneurosci.0545-13.2013
复制
发表时间：
2013-07-24
影响因子：
5.3
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
--
作者：
Sugawara, Takeyuki;Hisatsune, Chihiro;Mikoshiba, Katsuhiko
神经回路的结构维持对于成年后的高级大脑功能至关重要。虽然已经确定了几种分子作为海马和皮层神经元中棘维持的调节剂，但对浦肯野细胞（PC）棘如何在成熟小脑中维持知之甚少。在这里，我们表明，钙通道1型三磷酸肌醇受体（IP（3）R1）在PC中起着至关重要的作用，在控制平行纤维（PF）-PC突触回路在体内成熟小脑的维持。值得注意的是，在PC中缺乏IP（3）R1的成年小鼠（L7-Cre; Itpr 1（flox/flox））显示PC的棘密度和棘长度显著增加，尽管在发育期间具有正常的棘。此外，成熟小脑中异常重排的PF-PC突触回路在成年L7-Cre; Itpr 1（flox/flox）小鼠中引起意外严重的共济失调。我们的研究结果揭示了IP（3）R1在PC中的特殊作用，不仅作为小脑突触可塑性诱导的细胞内介质，而且作为体内成熟小脑PF-PC突触回路维持的关键调节剂;这种机制可能是成年人运动协调和学习的基础。
The structural maintenance of neural circuits is critical for higher brain functions in adulthood. Although several molecules have been identified as regulators for spine maintenance in hippocampal and cortical neurons, it is poorly understood how Purkinje cell (PC) spines are maintained in the mature cerebellum. Here we show that the calcium channel type 1 inositol trisphosphate receptor (IP(3)R1) in PCs plays a crucial role in controlling the maintenance of parallel fiber (PF)-PC synaptic circuits in the mature cerebellum in vivo. Significantly, adult mice lacking IP(3)R1 specifically in PCs (L7-Cre;Itpr1(flox/flox)) showed dramatic increase in spine density and spine length of PCs, despite having normal spines during development. In addition, the abnormally rearranged PF-PC synaptic circuits in mature cerebellum caused unexpectedly severe ataxia in adult L7-Cre; Itpr1(flox/flox) mice. Our findings reveal a specific role for IP(3)R1 in PCs not only as an intracellular mediator of cerebellar synaptic plasticity induction, but also as a critical regulator of PF-PC synaptic circuit maintenance in the mature cerebellum in vivo; this mechanism may underlie motor coordination and learning in adults.