Decreased level of histone acetylation in the infralimbic prefrontal cortex following immediate extinction may result in deficit of extinction memory

Abstract

In the last few decades, there has been exponential increase in studies aiming to trace the molecular mechanism of fear extinction with a hope to minimize the return of fear after exposure therapy required for operational treatment of anxiety disorders. The present study explored how the timing of extinction training after developing a specific fear, affects the consequent return of the extinguished fear and the role of histone acetylation in controlling the circuitry, thereof. It was found that rats undergone extinction training 10 min. after fear memory acquisition (Immediate Extinction) had deficits in retention of extinction memory as compared to one which underwent extinction 24 h after fear acquisition (Delayed Extinction). When the differences were sorted at the circuitry level the relative activity of the infralimbic prefrontal cortex (IL) to prelimbic cortex (PL) was found to be lower in the immediate extinction group as compared to the delayed extinction group as evidenced by the c-fos expression in the mPFC of these groups. Further investigation showed that acetylation of histone H3/H4 along with the levels of CREB binding protein (CBP) which is a histone acetyltransferase (HAT), was associated with neuronal activation and was significantly lower in the IL of the immediate extinction group than the delayed extinction group. In conclusion, the observed deficits in the immediate extinction group may be the result of compromised activation of IL, which in turn may be associated with changes in histone acetylation.