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. 2019 Apr 17:12:70.
doi: 10.3389/fnmol.2019.00070. eCollection 2019.

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

Affiliations

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

Ossama Khalaf et al. Front Mol Neurosci. .

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.

Keywords: basolateral amydala; engram; fear extinction; infralimbic cortex; memory trace; reconsolidation; remote memory; updating.

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Figures

Figure 1
Figure 1
Experimental setup to study brain areas involved in remote memory attenuation by catFISH. (A) Schematic representation of the two experimental groups used in the study. The lower part indicates the time course of the intracellular dynamics of the RNA transcripts Homer1A and cFos, which were employed in the catFISH experiment to study brain areas engaged in remote memory recall and after the massed extinction paradigm. (B) Behavioral results showing the efficiency of the massed extinction paradigm to attenuate remote fear memories (n = 8/group, p < 0.001). (C) Schematic representation of the brain structures selected for catFISH analysis as compared to the results obtained in the dentate gyrus (DG; Khalaf et al., 2018). (D,E) Schematic representation of the cortical and amygdalar substructures analyzed by catFISH, respectively. CFC, contextual fear conditioning; ACC, anterior cingulate cortex; BLA, basolateral amygdala; CeA, central amygdala; IL, infralimbic cortex; PL, prelimbic cortex. ***p < 0.001, two-tailed t-test.
Figure 2
Figure 2
catFISH-deduced engagement of amygdala subregions upon remote fear memory recall and attenuation. (A) Representative image of the mRNA transcripts Homer1a and cFos in the BLA upon remote fear memory attenuation. Scale bar = 5 μm. (B) Homer1a-deduced activation rate in the BLA (n = 8–10 mice/group, p < 0.01). (C) cFos-deduced extinction learning rate in the BLA (n = 8–13 mice/group, p < 0.05). (D) Reactivation rate in the BLA (n = 8–13 mice/group, p < 0.05). (E) Representative image of the mRNA transcripts Homer1a and cFos in the CeA upon remote fear attenuation. Scale bar = 5 μm. (F) Homer1a-deduced activation rate in the CeA (n = 8–13 mice/group, n.s.). (G) cFos-deduced extinction learning rate in the CeA (n = 8–13 mice/group, n.s.). (H) Reactivation rate in the CeA (n = 8–13 mice/group, n.s.). BLA, basolateral amygdala, CeA, central amygdala. **p < 0.01, two-tailed t-test; *p < 0.05, two-tailed t-test.
Figure 3
Figure 3
catFISH-deduced engagement of cortical subregions upon remote fear memory recall and attenuation. (A) Representative image of the mRNA transcripts Homer1a and cFos in the IL upon remote fear attenuation. Scale bar = 5 μm. (B) Homer1a-deduced activation rate in the IL (n = 5–9 mice/group, p = 0.0595). (C) cFos-deduced extinction learning rate in the IL (n = 5–6 mice/group, p < 0.05). (D) Reactivation rate in the IL (n = 5–6 mice/group, p < 0.05). (E) Representative image of the mRNA transcripts Homer1a and cFos in the PL upon remote fear attenuation. Scale bar = 5 μm. (F) Homer1a-deduced activation rate in the PL (n = 8–9 mice/group, n.s.). (G) cFos-deduced extinction learning rate in the PL (n = 8–9 mice/group, n.s.). (H) Reactivation rate in the PL (n = 8–9 mice/group, n.s.). (I) Representative image of the mRNA species Homer1a and cFos in the ACC upon remote fear attenuation. Scale bar = 5 μm. (J) Homer1a-deduced activation rate in the ACC (n = 8–9 mice/group, n.s.). (K) cFos-deduced extinction learning rate in the ACC (n = 4–8 mice/group, n.s.). (L) Reactivation rate in the ACC. (n = 4–8 mice/group, n.s.). ACC, anterior cingulate cortex; IL, infralimbic cortex; PL, prelimbic cortex. #p < 0.06; *p < 0.05, two-tailed t-test.

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References

    1. Albo Z., Gräff J. (2018). The mysteries of remote memory. Philos. Trans. R. Soc. B. Biol. Sci. 373:20170029. 10.1098/rstb.2017.0029 - DOI - PMC - PubMed
    1. Awad W., Ferreira G., Maroun M. (2015). Dissociation of the role of infralimbic cortex in learning and consolidation of extinction of recent and remote aversion memory. Neuropsychopharmacology 40, 2566–2575. 10.1038/npp.2015.103 - DOI - PMC - PubMed
    1. Bernier B. E., Lacagnina A. F., Ayoub A., Shue F., Zemelman B. V., Krasne F. B., et al. . (2017). Dentate gyrus contributes to retrieval as well as encoding: evidence from context fear conditioning, recall and extinction. J. Neurosci. 37, 6359–6371. 10.1523/JNEUROSCI.3029-16.2017 - DOI - PMC - PubMed
    1. Bontempi B., Laurent-Demir C., Destrade C., Jaffard R. (1999). Time-dependent reorganization of brain circuitry underlying long-term memory storage. Nature 400, 671–675. 10.1038/23270 - DOI - PubMed
    1. Bouton M. E. (2004). Context and behavioral processes in extinction. Learn. Mem. 11, 485–494. 10.1101/lm.78804 - DOI - PubMed

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