We recently reported that CaMKII-dependent phosphorylation of the neurofilament-L (NF-L) head domain was induced in the apical dendrites during long-term potentiation. Long-term depression (LTD) is another cellular model for neuronal plasticity. In the present study, we examined the phosphorylation of NF-L during hippocampal LTD using a series of phospho-specific antibodies against the NF-L head domain. During LTD, these antibodies visualized NF-L phosphorylation at Ser57 in the apical dendrites of the hippocampal pyramidal neurons. The assembly and disassembly of NF-L filaments are regulated by phosphorylation of its head domain. Thus, our results indicated that NF-L phosphorylation might be associated with alterations of the neuronal structure during LTD.