• Shaoli Wang, Tao Sheng, Siqiang Ren, Tian Tian, and Wei Lu.
• The Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China; Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
• Cell Rep. 2016 Aug 16; 16 (7): 1954-61.

AbstractPKMζ 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 (PKCι/λ), 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 PKCι/λ 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 PKCι/λ and PKMζ are detected during LTP or fear conditioning. Importantly, PKMζ, but not PKCι/λ, KD disrupts previously established LTM. Thus, PKCι/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 PKCs regulate the different stages of memory.Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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