Reactivation of Recall-Induced Neurons in the Infralimbic Cortex and the Basolateral Amygdala After Remote Fear Memory Attenuation.

Ossama Khalaf,Johannes Gräff

doi:10.3389/fnmol.2019.00070

Abstract

Whether the attenuation of traumatic memories is mediated through the suppression of the original memory trace of fear by a new memory trace of safety, or through an updating of the original fear trace towards safety has been a long-standing question at the interface of neuroscience and psychology. This matter is of particular importance for remote fear memories as they lie at the core of stress- and anxiety-related disorders. Recently, we have found that in the dentate gyrus, the effective attenuation of remote fear memories is accompanied by a reactivation of memory recall-induced neurons and that the continued activity of these neurons is critical for fear reduction. However, whether this also applies to other brain areas implicated in the storage of remote fear memories remains to be determined. Here, we show—by cellular compartment analysis of temporal activity using fluorescence in situ hybridization—that such reactivation also occurs in the basolateral amygdala and the infralimbic cortex, two brain areas known to be involved in fear memory attenuation. These results provide further experimental support for effective traumatic memory attenuation likely being mediated by an updating of the original fear trace towards safety.

Highlights

Post-traumatic stress and other anxiety disorders range among the most enduring forms of memories
Five minutes after the last extinction session, we identified neuronal populations activated at remote fear memory recall by the presence of cytoplasmic Homer1a mRNA transcripts, while the neuronal populations activated by extinction were visualized with nuclear cFos mRNA transcripts
We assessed extra-hippocampal brain areas implicated in remote memory storage, namely the amygdala and the prefrontal cortex (Kitamura et al, 2017; Figure 1C), more precisely the basolateral nucleus of the amygdala (BLA) and central amygdala (CeA; Figure 1D), as well as the anterior cingulate cortex (ACC), the PL and the IL (Figure 1E)

Summary

Introduction

Post-traumatic stress and other anxiety disorders range among the most enduring forms of memories. Because of the persistent nature of traumatic memories, early interventions are considered of prime importance (Davidson et al, 2004; Kearns et al, 2012). Such interventions are oftentimes not readily available, which places a strong emphasis on better understanding treatment approaches for remote traumata (McCleery and Harvey, 2004; Centonze et al, 2005).

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