ORIGINAL RESEARCH article
Front. Synaptic Neurosci.
Volume 17 - 2025 | doi: 10.3389/fnsyn.2025.1638371
PKMζ drives spatial memory reconsolidation but not maintenance
Provisionally accepted
João Rodrigo de Oliveira Rodrigo de Oliveira
Janine RossatoJohseph SouzaRodrigo OrvateLivia CarneiroAna Luizi Baracho
Martín Cammarota*- Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil
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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 ζinhibitory 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.
Keywords: Hippocampus, PKMζ, reconsolidation, spatial memory, memory maintenance, Amnesia
Received: 30 May 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 de Oliveira, Rossato, Souza, Orvate, Carneiro, Baracho and Cammarota. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Martín Cammarota, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN 59056-450, Brazil
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