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Objective Long term memory formation requires several signaling pathways activation and protein synthesis after learning, which is called consolidation.The classical opinion of the time-window of consolidation is approximately 6 hours, after which the newly formed memory transfers to be a stable long term memory.But lots of studies suggested that another protein synthesis-dependent phase happened later than consolidation, might determine the retention of long term memory.Recent evidences show that protein kinase Mζ (PKMζ), atypical kind of protein kinase C, play a critical role in the maintenance of long term memory.As a hippocampus (Hip)-dependent memory, contextual fear memory is a commonly used memory model, but the underlying molecular mechanism and role of Hip in memory retention are still not completely illustrated.The present study is to explore the role of PKMζ in.the retention of contextual fear memory.Methods The total PKMζ alteration was tested by Western Blot assays and Immunohistochemistry at the different time points after contextual fear conditioning.Long term memory was evaluated at the 10th day post-conditioning.The PKM inhibitor peptide was bilaterally intracranial microinjected to dorsal Hip at different time points to determine the role of PKMζ in the Hip.Results (1) The expression of PKMζ increased after 12 h following contextual fear conditioning but not 3 h, 6 h or 9 h after conditioning, and the effect endured to additional 12 h at least.(2) 12 h post-conditioning inhibition of PKMζ in dorsal Hip selectively impaired dayl 0 memory (tested on 10th day after conditioning) but not day2 memory.(3) Inhibit PKMζ immediately after contextual fear conditioning did not disrupt long term memory formation and retention.Conclusion Delayed synthesis of PKMζ in hippocampus after conditioning determines the retention of long term contextual fear memory.