Transcriptomic signatures of hippocampal active place avoidance memory maintenance.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Gene expression changes during memory acquisition, consolidation, and reconsolidation are well-understood in the hippocampus.
• However, the molecular changes during the offline maintenance of memory remain largely uncharacterized.
• Understanding these changes is crucial for comprehending long-term memory persistence.

Purpose of the Study:

• To investigate gene expression alterations in the dorsal hippocampus during the offline maintenance of a learned memory.
• To identify specific molecular changes in memory-associated neurons.
• To explore the transcriptomic landscape of hippocampal subregions during memory recall.

Main Methods:

• Spatial transcriptomics was employed on the dorsal hippocampus of mice 3 days after memory consolidation.
• The Arc-Cre/flox-eYFP transgenic mouse line was used to tag immediate early gene-expressing neurons.
• Single nuclear RNA sequencing was performed for high-resolution analysis of gene expression in specific neuronal populations.

Main Results:

• Spatially regionalized gene expression was observed, with specific functions enriched in CA1 (post-synaptic), CA3 (synaptic vesicle transport), and DG (neuronal differentiation).
• These enrichments were not found in the tagged memory-associated neurons (eYFP positive).
• Hippocampal neurons showed downregulated expression of genes involved in ATP synthesis and cytoplasmic translation, indicating reduced metabolic activity.

Conclusions:

• Offline memory maintenance involves distinct transcriptomic patterns, including regionally specific synaptic gene expression and reduced metabolic activity.
• Memory-associated neuronal ensembles may be sparsely distributed, despite regional gene expression changes.
• These findings provide novel insights into the molecular mechanisms underlying stable memory storage in the hippocampus.