Persistent increased PKM in long-term and remote spatial memory

PKM zeta is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKM zeta protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKM zeta during long-term memory has not been characterized. PKM zeta inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1 day to 1 month after training. Therefore, if the mechanisms of PKM zeta's persistent action in LTP maintenance and longterm memory were similar, persistent increases in PKM zeta would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKM zeta increases in dorsal hippocampus that persist from 1 day to 1 month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKW-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKM zeta sustains the kinase's action during long-term and remote spatial memory maintenance. (C) 2016 Published by Elsevier Inc.