Dual involvement of G-substrate in motor learning revealed by gene deletion.
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.
Endo
Shogo
S
Unit for Molecular Neurobiology of Learning and Memory, Okinawa Institute of Science and Technology, Uruma 904-2234, Japan.
Shutoh
Fumihiro
F
Dinh
Tung Le
TL
Okamoto
Takehito
T
Ikeda
Toshio
T
Suzuki
Michiyuki
M
Kawahara
Shigenori
S
Yanagihara
Dai
D
Sato
Yamato
Y
Yamada
Kazuyuki
K
Sakamoto
Toshiro
T
Kirino
Yutaka
Y
Hartell
Nicholas A
NA
Yamaguchi
Kazuhiko
K
Itohara
Shigeyoshi
S
Nairn
Angus C
AC
Greengard
Paul
P
Nagao
Soichi
S
Ito
Masao
M
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
C029152:G-substrate; D009419:Nerve Tissue Proteins