Impaired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice.
c-Jun N-terminal kinases (JNKs) are thought to be involved in regulating synaptic plasticity. We therefore investigated the specific role of JNK2 in modulating long-term potentiation (LTP) in hippocampus during development, using JNK2-deficient mice. The morphological structure and the numbers of both NeuN, a specific neuronal marker, and GABA-positive neurons in the hippocampal areas were similar in wild-type and Jnk2(-/-) mice. Western blot analysis revealed that JNK2 expression was higher and stable at 1 and 3 months of age, but JNK1 levels were lower at 1 month of age and almost undetectable in 3-month-old wild-type mice. In contrast to wild-type mice, there was a significant increase in JNK1 expression in JNK2 mutant mice, especially at 1 month of age. Electrophysiological studies demonstrated that LTP was impaired in both the CA1 and CA3 regions in 1-month-old, but not in adult, Jnk2(-/-) mice, probably owing to decreased presynaptic neurotransmitter release. Moreover, late-phase LTP, but not early-phase LTP, was impaired in the Jnk2(-/-) adult mice, suggesting that JNK2 plays a role in transforming early LTP to late LTP. Together, the data highlight the specific role of JNK2 in hippocampal synaptic plasticity during development.
Chen
Ju-Tao
JT
Department of Clinical Research, Singapore General Hospital, Singapore.
Lu
Da-Hua
DH
Chia
Chern-Pang
CP
Ruan
Di-Yun
DY
Sabapathy
Kanaga
K
Xiao
Zhi-Cheng
ZC
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006624:Hippocampus / Q000201:enzymology; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D048056:Mitogen-Activated Protein Kinase 9 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*
D048056:Mitogen-Activated Protein Kinase 9