Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts foreground context fear memory

Protein kinase Mzeta has been the subject of much recent interest, as it is the only molecule currently identified to maintain memory. Despite the wealth of studies investigating PKMζ in memory, questions remain about which types of memory PKMζ supports. Further, it is unclear how long the inhibitor of PKMz, ζ-pseudosubstrate inhibitory peptide (ZIP) remains in the brain after infusion. Here, we demonstrate that foreground context fear memory requires PKMζ activity in the amygdala. We also show that ZIP is fully cleared from the brain by 24 h after infusion. These data contribute to a growing body of literature that demonstrates that PKMζ plays a key role in maintaining amygdala-dependent memory and provides new information about the degradation timecourse of the most commonly used inhibitor of PKMζ, ZIP.

► We used ZIP to inhibit PKMζ in the amygdala 1 or 7 d after “foreground” context fear conditioning.
► We also used biotinylated ZIP to measure the degradation timecourse of ZIP.
► We found that PKMzeta is required to maintain context fear conditioning memory.
► ZIP is fully degraded from brain tissue by 24 h after intracranial infusion.