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Published on: January 5, 2018
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.
Abstract:
Non-reinforced reactivation destabilizes spatial memory in the Morris water maze (MWM), triggering reconsolidation, a protein synthesis-dependent process that restabilizes reactivated memories. PKMζ is a constitutively active, atypical PKC isoform implicated in memory storage. However, the potential involvement of this kinase in spatial memory reconsolidation remains unexplored. We found that intra-dorsal CA1 infusion of the PKMζ inhibitor myristoylated ζ-inhibitory peptide (ZIP), but not its inactive scrambled analog scZIP, following non-reinforced spatial memory reactivation in the MWM, induced time-dependent, long-lasting amnesia in adult male Wistar rats. This effect was replicated by silencing PKMζ mRNA translation with phosphorothioated antisense oligonucleotides, but not by inhibiting the related PKCι/λ with ICAP, and was prevented by disrupting hippocampal GluN2B-NMDAR signaling with RO25-6981, proteasome activity with clasto-lactacystin β-lactone, and AMPAR endocytosis with dynasore hydrate. ZIP had no effect on retention when given without reactivation or after reinforced reactivation. These findings suggest hippocampal PKMζ is necessary for spatial memory reconsolidation in the MWM, but not for its passive maintenance.
Insights
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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