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Publication : Dual involvement of G-substrate in motor learning revealed by gene deletion.

First Author  Endo S Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  9 Pages  3525-30
PubMed ID  19218432 Mgi Jnum  J:146808
Mgi Id  MGI:3838466 Doi  10.1073/pnas.0813341106
Citation  Endo S, et al. (2009) Dual involvement of G-substrate in motor learning revealed by gene deletion. Proc Natl Acad Sci U S A 106(9):3525-30
abstractText  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.
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