The different roles of cyclinD1-CDK4 in STP and mGluR-LTD during the postnatal development in mice hippocampus area CA1.
BACKGROUND
Cell-cycle-related proteins, such as cyclins or cyclin-dependent kinases, may have functions beyond that of cell cycle regulation. The expression and translocation of cyclinD1-CDK4 in post-mitotic neurons indicate that they may have supplementary functions in differentiated neurons that might be associated with neuronal plasticity.


RESULTS
In the present study, our findings showed that the expression of CDK4 was localized mostly in nuclei and cytoplasm of pyramidal cells of CA1 at postnatal day 10 (P10); whereas at P28 staining of CDK4 could be detected predominantly in the cytoplasm but not nuclei. Basal synaptic transmission was normal in the presence of CDK4 inhibitor. Short-term synaptic plasticity (STP) was impaired in CDK4 inhibitor pre-treated slices both from neonatal (P8-15) and adolescent (P21-35) animals; however there was no significant change in paired-pulse facilitation (PPF) in slices pre-incubated with the CDK4 inhibitor from adolescent animals. By the treatment of CDK4 inhibitor, the induction or the maintenance of Long-term potentiation (LTP) in response to a strong tetanus and NMDA receptor-dependent long-term depression (LTD) were normal in hippocampus. However, long-term depression (LTD) induced either by group I metabotropic glutamate receptors (mGluRs) agonist or by paired-pulse low-frequency stimulation (PP-LFS) was impaired in CDK4 inhibitor pretreated slices both from neonatal and adolescent animals. But the effects of the CDK4 inhibitor at slices from adolescent animals were not as robust as at slices from neonatal animals.


CONCLUSIONS
Our results indicated that the activation of cyclinD1-CDK4 is required for short-term synaptic plasticity and mGluR-dependent LTD, and suggested that this cyclin-dependent kinase may have different roles during the postnatal development in mice hippocampus area CA1.
Li
Chenchen
C
Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China. glacier@mail.ustc.edu.cn <glacier@mail.ustc.edu.cn>
Li
Xinmei
X
Chen
Weiheng
W
Yu
Shanshan
S
Chen
Jutao
J
Wang
Huili
H
Ruan
Diyun
D
D000818:Animals; D023902:Chromosome Pairing; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development*; D036881:Long-Term Synaptic Depression; D051379:Mice; D009473:Neuronal Plasticity; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
D056741:Cyclin D; D016213:Cyclins; D018094:Receptors, Metabotropic Glutamate; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4