c-Jun N-terminal phosphorylation is essential for hippocampal synaptic plasticity

c-Jun N-terminal kinase (INK), a member of the MAPK family, is an important regulatory factor of synaptic plasticity as well as neuronal differentiation and cell death. Recently, INK has been reported to modulate synaptic plasticity by the direct phosphorylation of synaptic proteins. The specific role of c-Jun phosphorylation in JNK mediated synaptic plasticity, however, remains unclear. In this study, we investigated the effects of c-Jun phosphorylation on synaptic structure and function by using c-Jun mutant mice, c-JunAA, in which the active phosphorylation sites at serines 63 and 73 were replaced by alanines. The gross hippocampal anatomy and number of spines on hippocampal pyramidal neurons were normal in c-JunAA mice. Basal synaptic transmission, input-output ratios, and paired-pulse facilitation (PPF) were also no different in c-JunAA compared with wild-type mice. Notably, however, the induction of long-term potentiation (LIP) at hippocampal CA3-CA1 synapses in c-JunAA mice was impaired, whereas induction of long-term depression (LTD) was normal. These data suggest that phosphorylation of the c-Jun N-terminus is required for LTP formation in the hippocampus, and may help to better characterize JNK-mediated modulation of synaptic plasticity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.