Spatially Resolved Transcriptomic Signatures of Hippocampal Subregions and Arc-Expressing Ensembles in Active Place...

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• The rodent hippocampus is crucial for spatial and episodic memory formation.
• Understanding gene expression changes during memory recall is key to deciphering memory mechanisms.

Approach:

• Bulk RNA sequencing and spatial transcriptomics were used to analyze gene expression in the dorsal hippocampus after active place avoidance (APA) memory recall.
• Gene expression patterns were examined across hippocampal subregions (CA1, CA3, DG) and within specific neuronal ensembles marked by immediate early genes (IEGs).

Key Points:

• Bulk RNA sequencing revealed distinct gene expression profiles in CA1/CA3 (synaptic transmission, plasticity) versus DG (energy balance, ribosomal function) following memory recall.
• Spatial transcriptomics identified transcriptionally and spatially distinct neuronal subpopulations marked by IEGs (Arc, Egr1, c-Jun).
• Differentially expressed genes between Arc+ and Arc- spots in trained mice were enriched in "regulation of synaptic plasticity" and "memory" gene ontology terms.

Conclusions:

• APA memory recall involves regionalized transcriptomic profiles within the dorsal hippocampus.
• Distinct IEG-expressing neuronal ensembles contribute to memory recall at a fine-grained transcriptional and spatial level.
• Synaptic plasticity is a key biological process differentiating neuronal ensembles involved in memory recall.