Abstract
There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.
Highlights
Fear extinction is defined as a lessening of conditioned fear responses following extinction training, during which subjects are exposed to repetitive presentations of conditioned stimuli (CS) alone (Pavlov, 1927; Bouton, 1988; Myers and Davis, 2007; Nader et al, 2013)
Single unit activities of a total of 72 neurons in the infralimbic cortex (IL) of 19 rats were recorded stably across the entire behavioral training (Figure 1—figure supplement 1A,B). These rats were subdivided into two groups based on the level of freezing during extinction recall, which was measured in the early part of the second extinction session and all single units obtained from each group were averaged for data analysis as previously described (Milad and Quirk, 2002)
In the successful extinction recall group, strong excitatory activities of the IL appeared during post-Ext1 (F4,220 = 3.346, p=0.0319, p
Summary
Fear extinction is defined as a lessening of conditioned fear responses following extinction training, during which subjects are exposed to repetitive presentations of conditioned stimuli (CS) alone (Pavlov, 1927; Bouton, 1988; Myers and Davis, 2007; Nader et al, 2013). Previous studies have provided numerous lines of evidence for the inhibition mechanism of fear extinction by which extinction training produces a new memory that inhibits the original fear memory stored in the lateral amygdala (LA) (Maren and Quirk, 2004; LeDoux, 2014). The neural circuits underlying the inhibition mechanism of fear extinction have been identified in the prefrontal cortex, the basolateral amygdala, the LA, and intercalated neurons (ITC) of the amygdala (Milad and Quirk, 2002; Chhatwal et al, 2005; Herry et al, 2008; Likhtik et al, 2008; Lin et al, 2009; Amano et al, 2010). The relative contribution of each mechanism to fear extinction needs to be determined
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