PDF(Pubmed)
Abstract：
The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP-EPAC-PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A-RIM1α-Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC-PKCε signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms.
摘要：
小脑参与精细运动技能的学习，然而，突触前可塑性是否有助于这种学习仍然难以捉摸。这里,我们报告说，EPAC-PKCε模块在小鼠小脑和运动行为的突触前长时程增强中具有关键作用。突触前cAMP-EPAC-PKCε信号级联诱导RIM1α的苏氨酸磷酸化，从而启动Rab3A-RIM1α-Munc13-1三方复合物的组装，该复合物有助于突触小泡的对接和释放。颗粒细胞特异性阻断EPAC-PKCε信号可以消除平行纤维与浦肯野细胞突触的突触前长时程增强作用，并损害小脑运动行为的基本表现和学习。这些结果揭示了突触前可塑性的功能相关性，它是通过一个新的信号级联调节的。从而丰富了小脑学习机制的频谱。
