Dual involvement of G-substrate in motor learning revealed by gene deletion
Dual involvement of G-substrate in motor learning revealed by gene deletion
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DOI：
10.1073/pnas.0813341106
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发表时间：
2009-03-03
影响因子：
11.1
通讯作者：
Ito, Masao
中科院分区：
文献类型：
--
作者：
Endo, Shogo;Shutoh, Fumihiro;Ito, Masao
在这项研究中，我们培养了缺乏g底物基因的小鼠，g底物是小脑浦肯野细胞中cgmp依赖性蛋白激酶的特异性底物，并探索了它们的特异性功能缺陷。出生后10-15周（PWs）获得的g底物缺乏的浦肯野细胞切片保持了与WT幼崽基本相似的电生理特性。平行纤维刺激与去极化脉冲相结合通常会引起长期抑制。然而，在较年轻的年龄，LTD在PW6时暂时减弱，此后恢复。与LTD平行，光动眼动反应（OKR）的短期（1 h）适应性在PW6时暂时减弱。在PW12下测试的年轻成年g底物敲除小鼠在脑结构、一般行为、转子杆或跑步机上的运动行为、眨眼条件反射、OKR动态特征或短期OKR适应方面与WT窝鼠没有显著差异。检测到的一个独特变化是在OKR的长期（5天）适应中出现了适度但显著的衰减。本研究结果支持了LTD是短期适应的因果关系的概念，并揭示了g底物在小脑短期和长期适应的神经元机制中的双重功能参与。
In this study, we generated mice lacking the gene for G-substrate, a specific substrate for cGMP-dependent protein kinase uniquely located in cerebellar Purkinje cells, and explored their specific functional deficits. G-substrate-deficient Purkinje cells in slices obtained at postnatal weeks (PWs) 10-15 maintained electrophysiological properties essentially similar to those from WT littermates. Conjunction of parallel fiber stimulation and depolarizing pulses induced long-term depression (LTD) normally. At younger ages, however, LTD attenuated temporarily at PW6 and recovered thereafter. In parallel with LTD, short-term (1 h) adaptation of optokinetic eye movement response (OKR) temporarily diminished at PW6. Young adult G-substrate knockout mice tested at PW12 exhibited no significant differences from their WT littermates in terms of brain structure, general behavior, locomotor behavior on a rotor rod or treadmill, eyeblink conditioning, dynamic characteristics of OKR, or short-term OKR adaptation. One unique change detected was a modest but significant attenuation in the long-term (5 days) adaptation of OKR. The present results support the concept that LTD is causal to short-term adaptation and reveal the dual functional involvement of G-substrate in neuronal mechanisms of the cerebellum for both short-term and long-term adaptation.