Coordination between Prefrontal Cortex Clock Gene Expression and Corticosterone Contributes to Enhanced Conditioned...

Area of Science:

• Neuroscience
• Chronobiology
• Behavioral Science

Background:

• Post-traumatic stress disorder (PTSD) is linked to impaired fear extinction and dysregulation of the ventromedial prefrontal cortex (vmPFC), circadian rhythms, and glucocorticoids.
• The vmPFC exhibits rhythmic clock gene expression, suggesting intrinsic circadian clock function influenced by corticosterone (CORT).

Purpose of the Study:

• To investigate the role of vmPFC clock gene expression and its interaction with CORT in auditory conditioned fear extinction learning.
• To determine if diurnal variations and CORT influence fear extinction recall.

Main Methods:

• Male rats were trained and tested during their active (night) or inactive (day) phases.
• vmPFC clock gene expression (Per1, Per2) was reduced using viral vectors.
• Circulating CORT levels were altered via adrenalectomy (ADX) with or without CORT replacement.

Main Results:

• Rats trained and tested at night showed superior fear extinction recall, which was impaired by vmPFC clock gene knockdown.
• Nighttime extinction recall was absent in ADX rats but restored with diurnal CORT and acute post-training CORT elevation.
• Fear extinction learning and recall are regulated diurnally.

Conclusions:

• Effective conditioned fear extinction requires intact vmPFC clock gene function and a combination of circadian and training-associated CORT.
• Targeting these mechanisms may enhance therapeutic outcomes for PTSD and related conditions.