Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice
Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice
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DOI：
10.1128/mcb.05208-11
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发表时间：
2011-07-01
影响因子：
5.3
通讯作者：
Morgan, James I.
中科院分区：
文献类型：
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作者：
Wei, Peng;Blundon, Jay A.;Morgan, James I.
PEP-19/PCP 4映射在唐氏综合征关键区域内，并编码一种小的、主要是神经元的IQ基序蛋白。Pep-19结合钙调蛋白并抑制钙调蛋白依赖性信号传导，这对突触功能至关重要，因此Pep-19水平的改变可能会影响突触可塑性和行为。为了研究其可能的作用，我们产生并表征pep-19/pcp 4-null小鼠。小脑浦肯野细胞兴奋性突触的突触可塑性，表达最高水平的Pep-19，显着改变pep-19/pcp 4-null小鼠。PEP-19/pcp 4基因敲除小鼠在平行纤维-浦肯野细胞突触处表现出长时程增强，而不是长时程抑制。突变小鼠在学习运动任务的能力上有明显的缺陷，这是通过在加速旋转杆上重复测试后提高的表现来衡量的。因此，我们的数据表明pep-19/pcp 4是小脑和运动学习中突触可塑性的关键决定因素。
PEP-19/PCP4 maps within the Down syndrome critical region and encodes a small, predominantly neuronal, IQ motif protein. Pep-19 binds calmodulin and inhibits calmodulin-dependent signaling, which is critical for synaptic function, and therefore alterations in Pep-19 levels may affect synaptic plasticity and behavior. To investigate its possible role, we generated and characterized pep-19/pcp4-null mice. Synaptic plasticity at excitatory synapses of cerebellar Purkinje cells, which express the highest levels of Pep-19, was dramatically altered in pep-19/pcp4-null mice. Instead of long-term depression, pep-19/pcp4-null mice exhibited long-term potentiation at parallel fiber-Purkinje cell synapses. The mutant mice have a marked deficit in their ability to learn a locomotor task, as measured by improved performance upon repeated testing on an accelerating rotarod. Thus, our data indicate that pep-19/pcp4 is a critical determinant of synaptic plasticity in cerebellum and locomotor learning.