Persistent increased PKMζ in long-term and remote spatial memory

Changchi Hsieh, Panayiotis Tsokas, Peter Serrano, A. Iván Hernández, Dezhi Tian, James E. Cottrell, Harel Z. Shouval, André Antonio Fenton, Todd Charlton Sacktor

Research output: Contribution to journalArticlepeer-review


PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1 day to 1 month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ 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 PKMζ 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 PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalNeurobiology of Learning and Memory
StatePublished - Feb 1 2017


  • LTP
  • Long-term potentiation
  • Memory
  • PKM-zeta
  • PKMzeta

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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