Different effects of low frequency stimulation to infralimbic prefrontal cortex on extinction of aversive memories

Experimental extinction is a behavioral technique in which animals learn to extinguish previously learned fear responses. The infralimbic cortex (IL) of the medial prefrontal cortex has an important role in extinction of aversive memories. We have recently shown that electrical stimulation of the IL in a form of high-frequency stimulation (HFS), which induces potentiation in the IL, was associated with enhanced ability to extinguish aversive memory in two aversive paradigms, the fear conditioning and the conditioned taste aversion paradigms. These results suggest that the induction of potentiation in the IL is associated with better ability to extinguish. In the present study we examined the opposite hypothesis that inducing depression in the IL by the application of low-frequency stimulation (LFS) will result in impairments in extinction. Our results show that the application of LFS to the IL retards extinction of fear conditioning only, suggesting that the application of LFS to the IL results in impairments in extinction of conditioned fear. In the conditioned taste aversion paradigm (CTA), LFS to the IL was associated with delayed enhancement of extinction of CTA that was apparent 48 h following stimulation. These results suggest that localized electrical stimulation to the IL may be an effective method for manipulating learned fear and affecting the ability to extinguish aversive associations.

► Fear and extinction are expressed in potentiation/ depression in the medial prefrontal cortex (mPFC).
► We have previously showed that the induction of potentiation in the mPFC results in enhanced extinction.
► In the present study we show that low frequency stimulation to the infralimbic cortex results in impaired extinction.
► Similar treatment but in conditioned taste aversion, non-fear based paradigm, results in facilitation in extinction.
► Altering plasticity in the medial prefrontal cortex could be of potential relevance to anxiety disorders.