Dissociation of the Role of Infralimbic Cortex in Learning and Consolidation of Extinction of Recent and Remote Aversion Memory

Abstract

Medial prefrontal circuits have been reported to undergo a major reorganization over time and gradually take a more important role for remote emotional memories such as contextual fear memory or food aversion memory. The medial prefrontal cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was also reported to be critical for recent memory extinction of contextual fear conditioning and conditioned odor aversion. However, its exact role in the extinction of remotely acquired information is still not clear. Using postretrieval blockade of protein synthesis or inactivation of the IL, we showed that the IL is similarly required for extinction consolidation of recent and remote fear memory. However, in odor aversion memory, the IL was only involved in extinction consolidation of recent, but not remote, memory. In contrast, only remote retrieval of aversion memory induced c-Fos activation in the IL and preretrieval inactivation of the IL with lidocaine impaired subsequent extinction of remote but not recent memory, indicating IL is necessary for extinction learning of remote aversion memory. In contrast to the effects in odor aversion, our data show that the involvement of the IL in the consolidation of fear extinction does not depend on the memory age. More importantly, our data indicate that the IL is implicated in the extinction of fear and nonfear-based associations and suggest dissociation in the engagement of the IL in the learning and consolidation of food aversion extinction over time.

A cFos activation map of remote fear memory attenuation

“…However, the involvement of its subregions in remote fear memory extinction remains elusive. While the roles of the infralimbic cortex (IL) and anterior cingulate cortex (ACC) were directly tested and showed controversial results (Vetere et al 2012 ; Rosas-Vidal et al 2014 ; Awad et al 2015 ), activity in the prelimbic cortex (PL) was never directly assessed during remote fear memory extinction despite its well-established role in the fear memory circuit (Frankland and Bontempi 2005 ). Moreover, specific molecular changes within the retrosplenial cortex (RSP) have been linked to remote fear memory extinction (Corcoran et al 2013 ).…”

“…Therefore, it is possible that the temporal shift in the circuits mediating memory retrieval is mirrored by an analogous shift in extinction circuits. For example, unlike the infralimbic cortex (IL), which is involved during both recent and remote extinction (Vetere et al 2012 ; Rosas-Vidal et al 2014 ; Awad et al 2015 ) molecular adaptations in the retrosplenial cortex are only necessary for remote extinction (Corcoran et al 2013 ).…”

Dysfunction in amygdala–prefrontal plasticity and extinction-resistant avoidance: A model for anxiety disorder vulnerability

“…This point was emphasized in a recent study comparing the role of the IL cortex in the extinction of two different aversive learning paradigms; contextual fear conditioning and conditioned odor aversion. The study found that while the IL cortex is necessary for the consolidation of extinction training of recent and remote contextual fear memories, it is only involved in the consolidation of extinction training for recent conditioned odor aversion (Awad et al, 2015). Thus, this study provides an example of how the same brain region could uniquely contribute to the extinction in two different aversive learning paradigms.…”

Neural oscillations in the infralimbic cortex after electrical stimulation of the amygdala. Relevance to acute stress processing

“…In these experiments it is noteworthy that theta power in the vmPFC specifically increases when the animal reaches the “safe” areas of anxiogenic environments, which has been interpreted as a mechanism for behavioural inhibition. In this context, IL theta rhythm seems to play a crucial role in fear extinction and stress control (Thompson et al, ; Awad, Ferreira, & Maroun, ; Ronzoni, Antón, Mora, Segovia, & Del Arco, ). Indeed corticolimbic theta coupling between the IL and the lateral amygdala has been described for fear extinction conditions, and is considered an example of adaptive inhibitory learning (Lesting et al, ).…”