Transcriptional Regulation Involved in Fear Memory Reconsolidation
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Memory reconsolidation has been demonstrated to offer a potential target period during which the fear memories underlying fear disorders can be disrupted. Reconsolidation is a labile stage that consolidated memories re-enter after memories are reactivated. Reactivated memories, induced by cues related to traumatic events, are susceptible to strengthening and weakening. Gene transcription regulation and protein synthesis have been suggested to be required for fear memory reconsolidation. Investigating the transcriptional regulation mechanisms underlying reconsolidation may provide a therapeutic method for the treatment of fear disorders such as post-traumatic stress disorder (PTSD). However, the therapeutic effect of treating a fear disorder through interfering with reconsolidation is still contradictory. In this review, we summarize several transcription factors that have been linked to fear memory reconsolidation and propose that transcription factors, as well as related signaling pathways can serve as targets for fear memory interventions. Then, we discuss the application of pharmacological and behavioral interventions during reconsolidation that may or not efficiently treat fear disorders.
KeywordsFear memory Reconsolidation Transcriptional factor Post-traumatic stress disorder
This work was supported by the National Science Foundation of China (NSFC, No. 31500896) and Natural Science Foundation Project of CQ (cstc2016jcyjA0587).
Compliance with ethical standards
Conflicts of Interest
The authors declare that they have no conflicts of interest.
- Barbosa AC, Kim MS, Ertunc M, Adachi M, Nelson ED, McAnally J, Richardson JA, Kavalali ET, Monteggia LM, Bassel-Duby R, Olson EN (2008) MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function. Proc Natl Acad Sci U S A 105:9391–9396PubMedPubMedCentralCrossRefGoogle Scholar
- Cadigan KM, Waterman ML (2012) TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol 4Google Scholar
- French PJ, O’Connor V, Jones MW, Davis S, Errington ML, Voss K, Truchet B, Wotjak C, Stean T, Doyere V, Maroun M, Laroche S, Bliss TV (2001) Subfield-specific immediate early gene expression associated with hippocampal long-term potentiation in vivo. Eur J Neurosci 13:968–976PubMedCrossRefGoogle Scholar
- Gamache K, Pitman RK, Nader K (2012) Preclinical evaluation of reconsolidation blockade by clonidine as a potential novel treatment for posttraumatic stress disorder. Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology 37:2789PubMedPubMedCentralCrossRefGoogle Scholar
- Kindt M, Soeter M, Sevenster D (2014) Disrupting reconsolidation of fear memory in humans by a noradrenergic beta-blocker. J Vis Exp. https://doi.org/10.3791/52151
- Liu JF, Yang C, Deng JH, Yan W, Wang HM, Luo YX, Shi HS, Meng SQ, Chai BS, Fang Q, Chai N, Xue YX, Sun J, Chen C, Wang XY, Wang JS, Lu L (2015) Role of hippocampal beta-adrenergic and glucocorticoid receptors in the novelty-induced enhancement of fear extinction. J Neurosci 35:8308–8321PubMedCrossRefGoogle Scholar
- Lv XF, Sun LL, Cui CL, Han JS (2015) NAc shell Arc/Arg3.1 protein mediates reconsolidation of morphine CPP by increased GluR1 cell surface expression: activation of ERK-coupled CREB is required. Int J Neuropsychopharmacol 18Google Scholar
- Machado I, Gonzalez PV, Vilcaes A, Carniglia L, Schioth HB, Lasaga M, Scimonelli TN (2015) Interleukin-1beta-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and alpha-melanocyte-stimulating hormone prevented these effects. Brain Behav Immun 46:137–146PubMedCrossRefGoogle Scholar
- Milton AL, Lee JL, Butler VJ, Gardner R, Everitt BJ (2008) Intra-amygdala and systemic antagonism of NMDA receptors prevents the reconsolidation of drug-associated memory and impairs subsequently both novel and previously acquired drug-seeking behaviors. J Neurosci 28:8230–8237PubMedCrossRefGoogle Scholar
- Morice E, Farley S, Poirier R, Dallerac G, Chagneau C, Pannetier S, Hanauer A, Davis S, Vaillend C, Laroche S (2013) Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin-Lowry syndrome. Neurobiol Dis 58:156–168PubMedCrossRefGoogle Scholar
- Ren J, Li X, Zhang X, Li M, Wang Y, Ma Y (2013) The effects of intra-hippocampal microinfusion of D-cycloserine on fear extinction, and the expression of NMDA receptor subunit NR2B and neurogenesis in the hippocampus in rats. Prog Neuropsychopharmacol Biol Psychiatry 44:257–264PubMedCrossRefGoogle Scholar
- Rothbaum BO, Kearns MC, Price M, Malcoun E, Davis M, Ressler KJ, Lang D, Houry D (2012) Early intervention may prevent the development of posttraumatic stress disorder: a randomized pilot civilian study with modified prolonged exposure. Biol Psychiatry 72:957–963PubMedPubMedCentralCrossRefGoogle Scholar
- Saridogan GE, Aykac A, Cabadak H, Cerit C, Caliskan M, Goren MZ (2015) D-Cycloserine acts via increasing the GluN1 protein expressions in the frontal cortex and decreases the avoidance and risk assessment behaviors in a rat traumatic stress model. Behav Brain Res 293:227–233PubMedCrossRefGoogle Scholar
- Sekeres MJ, Mercaldo V, Richards B, Sargin D, Mahadevan V, Woodin MA, Frankland PW, Josselyn SA (2012) Increasing CRTC1 function in the dentate gyrus during memory formation or reactivation increases memory strength without compromising memory quality. J Neurosci 32:17857–17868PubMedCrossRefGoogle Scholar
- Tedesco V, Roquet RF, DeMis J, Chiamulera C, Monfils MH (2014) Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala. Neurobiol Learn Mem 115:78–85PubMedCrossRefGoogle Scholar