Sex differences in auditory fear discrimination are associated with altered medial prefrontal cortex function

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Psychiatry

Background:

• Post-traumatic stress disorder (PTSD) is more prevalent in women, potentially due to sex differences in fear inhibition and medial prefrontal cortex (mPFC) function.
• PTSD involves fear overgeneralization and impaired regulation by safety signals.
• Previous research indicated sex differences in fear generalization and reduced safety signaling in females after fear discrimination training.

Purpose of the Study:

• To investigate whether observed sex differences in learned fear inhibition are associated with altered medial prefrontal cortex (mPFC) function.
• To determine the role of prelimbic (PL) and infralimbic (IL) mPFC activity during fear retrieval and safety signaling.

Main Methods:

• Male and female rats underwent three days of auditory fear discrimination training (CS+ paired with footshock, CS- presented alone).
• Local field potentials were recorded from the prelimbic (PL) and infralimbic (IL) mPFC during fear retrieval.
• Behavioral responses (freezing) and neural oscillations (theta and gamma) were analyzed.

Main Results:

• Females exhibited fear generalization, while males showed fear discrimination based on cue-induced freezing.
• Sex differences in basal theta and gamma oscillations were observed in the PL and IL mPFC.
• Males displayed PL/IL theta activation during safety signaling (CS-) and IL gamma activation to threat (CS+), which were absent in females.

Conclusions:

• Sex differences in learned fear inhibition are linked to distinct medial prefrontal cortex (mPFC) functional activity.
• Altered mPFC oscillatory patterns may underlie sex-specific fear generalization and impaired safety signaling in PTSD.
• These findings contribute to understanding the neurobiological basis of sex differences in PTSD.