ReviewDoes PKM(zeta) maintain memory?

- We review the state of the literature on PKMζ and memory maintenance.
- Research both for and against the idea that PKMζ maintains memory is presented.
- PKMζ may maintain memory or may be a restabilization mechanism.
- Future directions for the memory maintenance field are presented.

Work on the long-term stability of memory has identified a potentially critical role for protein kinase Mzeta (PKMζ) in maintaining established memory. PKMζ, an autonomously active isoform of PKC, is hypothesized to sustain those changes that occurred during memory formation in order to preserve the memory engram over time. Initial studies investigating the role of PKMζ were largely successful in demonstrating a role for the kinase in memory maintenance; disrupting PKMζ activity with ζ-inhibitory peptide (ZIP) was successful in disrupting a variety of established associations in a number of key brain regions. More recent work, however, has questioned both the role of PKMζ in memory maintenance and the effectiveness of ZIP as a specific inhibitor of PKMζ activity. Here, we outline the research both for and against the idea that PKMζ is a memory maintenance mechanism and discuss how these two lines of research can be reconciled. We conclude by proposing a number of studies that would help to clarify the role of PKMζ in memory and define other mechanisms the brain may use to maintain memory.