Geon The Maintenance of LTP by PKMζ Papers

 

Abstract

This paper reviews evidence for the role of PKMζ in maintaining long-term potentiation (LTP) and discusses whether or not the very long term memory (VLTM, > 1 month) is stored in PKMζ. The LTP induction may cause protein kinase A (PKA) to translocate from spines to the nucleus, triggering expression of the brain-derived neurotrophic factor (BDNF), which subsequently induces production of plasticity-related proteins, including PKMζ - a persistently active atypical protein kinase C (aPKC). Once synthesized near the synapse, the active PKMζ may up-regulate the GluA2-containing AMPARs to maintain LTP. On the other hand, the translation of PKMζ is negatively regulated by the α-subunit of eukaryotic initiation factor 2 (eIF2α), which in turn is controlled by protein kinase-like ER kinase (PERK). PKMζ was thought to store VLTM based on the finding that its inhibitor, zeta inhibitory peptide (ZIP), abolishes the memory of conditioned taste aversion even 3 mo after encoding (Shema et al., 2009). Recent studies suggest that the ZIP dosage used by Shema et al. could also inhibit PKCλ, thereby disrupting microtubule transport of PSD-95. According to the Microtubule Track (MTT) hypothesis for VLTM, disruption of PSD-95 trafficking along specific MTTs should abolish the memory.

 

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