Strain Differences in Responsiveness to Repeated Restraint Stress Affect Remote Contextual Fear Memory and Blood...

Area of Science:

• Neuroscience
• Behavioral Biology
• Molecular Biology

Background:

• The impact of stress on fear memory consolidation and retrieval remains incompletely understood.
• Individual differences in stress reactivity suggest varied responses to stressful events.
• Stress is known to modulate fear memory, but the mechanisms underlying strain-specific effects require elucidation.

Purpose of the Study:

• To investigate how chronic stress affects fear memory in rat strains with differing stress-reactivity.
• To identify molecular mechanisms, via blood transcriptomics, underlying strain-specific stress responses.
• To explore the relationship between stress-induced changes in gene expression and fear memory alterations.

Main Methods:

• Utilized the contextual fear conditioning (CFC) paradigm in Fisher 344 (F344) and Wistar-Kyoto (WKY) rats.
• Administered chronic restraint stress (CRS) or no stress (NS) for two weeks prior to a second CFC.
• Performed RNA sequencing on blood samples to analyze differentially expressed genes (DEGs) between stressed and non-stressed groups.

Main Results:

• Recent and reinstated fear memory were higher in F344 rats compared to WKY rats, irrespective of stress exposure.
• Remote fear memory was attenuated in F344 rats following CRS, but not in WKY rats.
• Overlapping DEGs in blood suggested conserved stress response pathways, while unique DEGs indicated divergent molecular networks influenced by stress-reactivity.

Conclusions:

• Chronic stress can attenuate previously formed fear memories, particularly in individuals with average stress reactivity.
• Novel blood-borne DEGs may serve as biomarkers for an individual's general stress state or stress-responsiveness.
• Strain-specific transcriptomic changes highlight distinct molecular adaptations to stress beyond inherent differences.