1. Dual involvement of G-substrate in motor learning revealed by gene deletion
- Author
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Endo, Shogo, Shutoh, Fumihiro, Le Dinh, Tung, Okamoto, Takehito, Ikeda, Toshio, Suzuki, Michiyuki, Kawahara, Shigenori, Yanagihara, Dai, Sato, Yamato, Yamada, Kazuyuki, Sakamoto, Toshiro, Kirino, Yutaka, Hartell, Nicholas A., Yamaguchi, Kazuhiko, Itohara, Shigeyoshi, Nairn, Angus C., Greengard, Paul, Nagao, Soichi, and Ito, Masao
- Subjects
Chromosome deletion -- Research ,Gene expression -- Research ,Purkinje cells -- Research ,Nystagmus -- Research ,Neural transmission -- Regulation ,Neural transmission -- Research ,Science and technology - Abstract
In this study, we generated mice lacking the gene for G-substrata, 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 (1h) 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. cerebellum | long-term depression | optokinetic response | Purkinje cell
- Published
- 2009