Abstract
The increased prevalence of post-traumatic stress disorder (PTSD) that is observed in women may involve sex differences in learned fear inhibition and medial prefrontal cortex (mPFC) function. PTSD is characterized by fear overgeneralization involving impaired fear regulation by safety signals. We recently found that males show fear discrimination and females show fear generalization involving reduced safety signalling after extended fear discrimination training. Here we determined if these sex differences involve altered mPFC function. Male and female rats underwent three days of auditory fear discrimination training, where one tone (CS+) was paired with footshock and another tone (CS−) was presented alone. Local field potentials were recorded from prelimbic (PL) and infralimbic (IL) mPFC during retrieval. We found that males discriminated and females generalized based on cue-induced freezing at retrieval. This was accompanied by sex differences in basal theta and gamma oscillations in PL and IL. Importantly, males also showed PL/IL theta activation during safety signalling by the CS− and IL gamma activation in response to the threat-related CS+, both of which were absent in females. These results add to growing evidence indicating that sex differences in learned fear inhibition are associated with altered mPFC function.
Highlights
The increased prevalence of post-traumatic stress disorder (PTSD) that is observed in women may involve sex differences in learned fear inhibition and medial prefrontal cortex function
Post-hoc analysis indicated that males showed significantly increased freezing during the CS+, compared to the CS− (P < 0.0001), while females showed no difference in freezing between the two cues (P > 0.05)
These results suggest that females show fear generalization after three days of discrimination training
Summary
The increased prevalence of post-traumatic stress disorder (PTSD) that is observed in women may involve sex differences in learned fear inhibition and medial prefrontal cortex (mPFC) function. We found that males discriminated and females generalized based on cue-induced freezing at retrieval This was accompanied by sex differences in basal theta and gamma oscillations in PL and IL. Males showed PL/IL theta activation during safety signalling by the CS− and IL gamma activation in response to the threat-related CS+, both of which were absent in females These results add to growing evidence indicating that sex differences in learned fear inhibition are associated with altered mPFC function. We recently showed in rats that males display auditory fear discrimination after extended discrimination training, whereas females exhibit www.nature.com/scientificreports fear generalization involving reduced safety signalling[26]. After extended auditory fear discrimination training, we recorded local field potentials (LFPs) in mPFC during retrieval testing to determine if discrimination and generalization in males and females, respectively, are characterized by sex differences in mPFC function. As there is evidence for distinct contributions of PL and IL to fear discrimination[29,36], we recorded LFPs from both of these mPFC subregions at retrieval
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