Distinct Roles of PKCι/λ and PKMζ in the Initiation and Maintenance of Hippocampal Long-Term Potentiation and Memory.

PKMζ has been proposed to be essential for maintenance of long-term potentiation (LTP) and long-term memory (LTM). However, recent data from PKMζ-knockout mice has called this role into question. Instead, the other atypical isoform, protein kinase C iota/lambda has emerged as a potential alternative player. Therefore, the nature of the "memory molecule" maintaining learned information remains uncertain. Here, we report knockdown (KD) of and PKMζ in the dorsal hippocampus and find deficits in early expression and late maintenance, respectively, during both LTP and hippocampus-dependent LTM. Sequential increases in the active form of duanyu1531ι/λ and PKMζ are detected during LTP or fear conditioning. Importantly, PKMζ, but not KD disrupts previously established LTM. Thus, duanyu1531ι/λ and PKMζ have distinct functions in LTP and memory, with PKMζ playing a specific role in memory maintenance. This relaying pattern may represent a precise molecular mechanism by which atypical regulate the different stages of memory.

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