αCaMKII is essential for cerebellar LTD and motor learning
αCaMKII is essential for cerebellar LTD and motor learning
复制标题
DOI：
10.1016/j.neuron.2006.08.013
复制
发表时间：
2006-09-21
期刊：
影响因子：
16.2
通讯作者：
Elgersma, Ype
中科院分区：
文献类型：
--
作者：
Hansel, Christian;de Jeu, Marcel;Elgersma, Ype
突触后α-钙离子/钙调素依赖性蛋白激酶II（α CaMKII）的钙内流的激活是诱导长时程增强（LTP）在大多数兴奋性突触在海马和皮层的先决条件。在这里，我们表明，突触后UP是不受影响的平行纤维浦肯野细胞突触在小脑的α CaMK Ⅱ-/-小鼠。相比之下，长期抑郁症（LTD）的协议只导致短暂的抑郁症在青少年α CaMKII-/-突变体和强大的增强成年突变体。这表明，在平行纤维浦肯野细胞可塑性的功能α CaMK Ⅱ是相反的兴奋性海马和皮质突触的功能。此外，α CaMKII-/-小鼠显示前庭眼反射和视动反射的增益增加适应受损。由于浦肯野细胞是小脑中唯一表达α CaMKII的细胞，我们的数据表明，平行纤维LTD的损伤，同时保持UP完整，足以破坏这种形式的小脑学习。
Activation of postsynaptic alpha-calclum/calmodulin-dependent protein kinase II (alpha CaMKII) by calcium influx is a prerequisite for the induction of long-term potentiation (LTP) at most excitatory synapses in the hippocampus and cortex. Here we show that postsynaptic UP is unaffected at parallel fiber-Purkinje cell synapses in the cerebellum of alpha CaMKII-/- mice. In contrast, a long-term depression (LTD) protocol resulted in only transient depression in juvenile alpha CaMKII-/- mutants and in robust potentiation in adult mutants. This suggests that the function of alpha CaMKII in parallel fiber-Purkinje cell plasticity is opposite to its function at excitatory hippocampal and cortical synapses. Furthermore, alpha CaMKII-/- mice showed impaired gain-increase adaptation of both the vestibular ocular reflex and optokinetic reflex. Since Purkinje cells are the only cells in the cerebellum that express alpha CaMKII, our data suggest that an impairment of parallel fiber LTD, while leaving UP intact, is sufficient to disrupt this form of cerebellar learning.