Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

Kristoffer Højgaard, Bianka Szöllősi, Kim Henningsen, Natsumi Minami, Nobuhiro Nakanishi, Erik Kaadt, Makoto Tamura, Richard G.M. Morris, Tomonori Takeuchi*, Betina Elfving*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role for Agap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription of Agap3 may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5 receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.

Original languageEnglish
Article number69
JournalMolecular Brain
Number of pages14
Publication statusPublished - Dec 2023


  • AGAP3
  • Behavioural tagging
  • Dopamine
  • Dopamine receptor antagonist
  • Hippocampus
  • Immediate-early gene
  • Locus coeruleus
  • Memory consolidation
  • Novelty
  • Synaptic tagging and capture hypothesis


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