Circadian Rhythms in Conditioned Threat Extinction Reflect Time-of-Day Differences in Ventromedial Prefrontal Cortex...

Area of Science:

• Neuroscience
• Chronobiology
• Behavioral Science

Background:

• Circadian rhythms regulate various physiological processes, including memory.
• The ventromedial prefrontal cortex (vmPFC) contains a local circadian clock crucial for conditioned threat extinction.
• The precise mechanisms by which this local clock influences extinction-related neural adaptations remain largely unknown.

Purpose of the Study:

• To investigate how the local circadian clock in the rat vmPFC contributes to extinction-dependent neural and behavioral plasticity.
• To examine the time-of-day-dependent neural activity patterns in the vmPFC during conditioned threat extinction.

Main Methods:

• Single-unit and local field potential recordings were performed in the male rat vmPFC.
• Neural activity was analyzed during repeated extinction sessions conducted at different times of day.
• Neuronal firing patterns, oscillatory coupling, and phase-locking were assessed in relation to behavior (freezing vs. mobility).

Main Results:

• Superior recall of remote extinction memory was observed during the circadian active phase.
• vmPFC principal neurons showed amplified cue-evoked firing and diminished freezing-transition firing during the active phase.
• Increased coupling of vmPFC gamma amplitude to low-frequency oscillations during freezing, augmented during the active phase, indicated time-of-day-dependent cell assembly organization.
• A higher proportion of vmPFC neurons were phase-locked to low-frequency oscillations during the active phase, suggesting heightened neural excitability.

Conclusions:

• Daily fluctuations in vmPFC excitability, driven by the local circadian clock, enhance neural recruitment into extinction-related cell assemblies during the active phase.
• This provides a potential mechanism for how the vmPFC local clock modulates neural and behavioral plasticity during conditioned threat extinction.
• The findings highlight the critical role of circadian timing in fear extinction and memory regulation.