Abstract
Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including the infralimbic cortex (IL), immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS) of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA). IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion.
Highlights
Experimental extinction is the decline in the frequency or intensity of a conditioned response following the withdrawal of reinforcement, and is believed to reflect relearning rather than unlearning [1,2,3,4]
The main finding of the current study was that high-frequency stimulation (HFS) of the infralimbic subregion (IL) following retrieval of a conditioned fear memory led to significant reductions in fear during extinction
Another novel finding was that the same effect of IL-HFS was produced in a conditioned taste aversion (CTA) paradigm
Summary
Experimental extinction is the decline in the frequency or intensity of a conditioned response following the withdrawal of reinforcement, and is believed to reflect relearning rather than unlearning [1,2,3,4]. A reduced ability to extinguish conditioned fear associations might contribute to the persistence of maladaptive fear in conditions such as posttraumatic stress disorder (PTSD) and may reduce the effectiveness of therapeutic interventions that rely on extinction processes [5,6,7,8]. The infralimbic subregion (IL) of medial prefrontal cortex (mPFC) has been suggested to play a key role in extinction of aversive associations as measured using Pavlovian conditioned fear and taste aversion paradigms [9,10,11,12,13,14,15,16]. High-frequency stimulation (HFS) of the mediodorsal thalamic inputs to the mPFC, including IL, immediately prior to extinction learning facilitates extinction memory in mice, whereas low-frequency stimulation has the opposite effect [20,21]. Extinction is associated with plasticity changes in inputs from, as well as outputs to, the basolateral amygdala (BLA), in the form of augmentation of evoked field potentials (EFPs) in the BLAmPFC pathway and depression of EFPs in the reciprocal mPFCBLA pathway [22]
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