Skip to Main content Skip to Navigation
Journal articles

The histone H3 lysine 9 methyltransferase G9a/GLP complex activity is required for long-term consolidation of spatial memory in mice

Abstract : The G9a/G9a-like protein (GLP) histone lysine dimethyltransferase complex and downstream histone H3 lysine 9 dimethylation (H3K9me2) repressive mark have recently emerged as key transcriptional regulators of gene expression programs necessary for long-term memory (LTM) formation in the dorsal hippocampus. However, the role for hippocampal G9a/GLP complex in mediating the consolidation of spatial LTM remains largely unknown. Using a water maze competition task in which both dorsal hippocampus-dependent spatial and striatum-dependent cue navigation strategies are effective to solve the maze, we found that pharmacological inhibition of G9a/GLP activity immediately after learning disrupts long-term consolidation of previously learned spatial information in male mice, hence producing cue bias on the competition test performed 24 h later. Importantly, the inhibition of hippocampal G9a/GLP did not disrupt short-term memory retention. Immunohistochemical analyses revealed increases in global levels of permissive histone H3K9 acetylation in the dorsal hippocampus and dorsal striatum at 1 h post-training, which persisted up to 24 h in the hippocampus. Conversely, H3K9me2 levels were either unchanged in the dorsal hippocampus or transiently decreased at 15 min post-training in the dorsal striatum. Finally, the inhibition of G9a/GLP activity further increased global levels of H3K9 acetylation while decreasing H3K9me2 in the hippocampus at 1 h post-training. However, both marks returned to vehicle control levels at 24 h. Together, these findings support the possibility that G9a/GLP in the dorsal hippocampus is required for the transcriptional switch from short-term to long-term spatial memory formation
Complete list of metadata

https://hal-cnrs.archives-ouvertes.fr/hal-03422574
Contributor : Nicole Mons Connect in order to contact the contributor
Submitted on : Monday, November 22, 2021 - 10:31:27 AM
Last modification on : Monday, November 22, 2021 - 4:11:02 PM

File

Nicolay-Kritter et al.fevrier2...
Files produced by the author(s)

Identifiers

Collections

Citation

Kyrian Nicolay-Kritter, Jordan Lassalle, Jean-Louis Guillou, N Mons. The histone H3 lysine 9 methyltransferase G9a/GLP complex activity is required for long-term consolidation of spatial memory in mice. Neurobiology of Learning and Memory, Elsevier, 2021, 179, pp.107406. ⟨10.1016/j.nlm.2021.107406⟩. ⟨hal-03422574⟩

Share

Metrics

Les métriques sont temporairement indisponibles