title: Dual involvement of G-substrate in motor learning revealed by gene deletion.
abstract: 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.
authors.affiliation: Unit for Molecular Neurobiology of Learning and Memory, Okinawa Institute of Science and Technology, Uruma 904-2234, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Endo
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Shutoh
authors.forename: Tung Le
authors.initials: TL
authors.lastname: Dinh
authors.forename: Takehito
authors.initials: T
authors.lastname: Okamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Ikeda
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kawahara
authors.forename: Dai
authors.initials: D
authors.lastname: Yanagihara
authors.forename: Yamato
authors.initials: Y
authors.lastname: Sato
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kirino
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Hartell
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
authors.forename: Soichi
authors.initials: S
authors.lastname: Nagao
authors.forename: Masao
authors.initials: M
authors.lastname: Ito
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D007858:Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015835:Ocular Motility Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C029152:G-substrate; D009419:Nerve Tissue Proteins