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PKMζ drives spatial memory reconsolidation but not maintenance
João Rodrigo de Oliveira1, Janine I Rossato1, Johseph P G Souza1
1Memory Research Laboratory, Brain Institute, UFRN, Natal, Brazil.
Frontiers in Synaptic Neuroscience
|August 29, 2025
Summary
Protein kinase M zeta (PKMζ) is crucial for reconsolidating spatial memory in the Morris water maze (MWM). Inhibiting PKMζ after memory reactivation causes long-lasting amnesia in rats.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Neuroscience
Background:
- Spatial memory destabilization and reconsolidation are key processes for memory restabilization.
- Protein kinase M zeta (PKMζ) is implicated in memory storage but its role in reconsolidation is unknown.
Purpose of the Study:
- To investigate the role of PKMζ in the reconsolidation of spatial memory.
- To determine if PKMζ is necessary for the maintenance of spatial memory.
Main Methods:
- Infusion of PKMζ inhibitor (ZIP) or control into the dorsal CA1 region of Wistar rats.
- Non-reinforced reactivation of spatial memory in the Morris water maze (MWM).
- Assessment of amnesia using behavioral tasks and molecular inhibition techniques (antisense oligonucleotides, specific pathway inhibitors).
Main Results:
- Intra-dorsal CA1 infusion of ZIP, but not scZIP, induced time-dependent, long-lasting amnesia after memory reactivation.
- PKMζ mRNA translation silencing replicated the amnesic effect; inhibition of related PKC isoforms did not.
- Disruption of hippocampal GluN2B-NMDAR, proteasome activity, or AMPAR endocytosis prevented ZIP-induced amnesia.
- ZIP did not affect memory retention without reactivation or after reinforced reactivation.
Conclusions:
- Hippocampal PKMζ is essential for the reconsolidation of spatial memory in the MWM.
- PKMζ is not required for the passive maintenance of spatial memory.
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