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Disruption of AMPA receptor endocytosis impairs the extinction, but not acquisition of learned fear.
Neuropsychopharmacology. 2008 Sep; 33(10):2416-26.N

Abstract

Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in the suppression of a learned fear response remains to be clarified. Here, we assessed the role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2(3Y); 1.5 micromol/kg, i.v.) that blocks regulated alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor endocytosis during an initial extinction training session disrupted both the expression and recall of extinction learning. A similar impairment of extinction during training, but not recall, was observed when NMDA receptor-dependent LTD was inhibited through the selective blockade of NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat-GluR2(3Y) during fear conditioning or during a fear recall test did not effect the expression or recall of either contextual or cue-induced conditioned fear. Similarly, administration of Tat-GluR2(3Y) prior to an extinction recall test did not affect spontaneous recovery or rate of re-extinction in previously extinguished rats. These data demonstrate that AMPA receptor endocytosis does not mediate acquisition or expression of conditioned fear, but may play a role in the extinction of fear memories. Furthermore, these findings suggest that LTD may be a molecular mechanism that facilitates the selective modification of a learned association while leaving intact the ability to form a new memory.

Authors+Show Affiliations

Department of Psychology, University of British Columbia, Vancouver, BC, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18046303

Citation

Dalton, Gemma L., et al. "Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but Not Acquisition of Learned Fear." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 33, no. 10, 2008, pp. 2416-26.
Dalton GL, Wang YT, Floresco SB, et al. Disruption of AMPA receptor endocytosis impairs the extinction, but not acquisition of learned fear. Neuropsychopharmacology. 2008;33(10):2416-26.
Dalton, G. L., Wang, Y. T., Floresco, S. B., & Phillips, A. G. (2008). Disruption of AMPA receptor endocytosis impairs the extinction, but not acquisition of learned fear. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 33(10), 2416-26.
Dalton GL, et al. Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but Not Acquisition of Learned Fear. Neuropsychopharmacology. 2008;33(10):2416-26. PubMed PMID: 18046303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disruption of AMPA receptor endocytosis impairs the extinction, but not acquisition of learned fear. AU - Dalton,Gemma L, AU - Wang,Yu Tian, AU - Floresco,Stan B, AU - Phillips,Anthony G, Y1 - 2007/11/28/ PY - 2007/11/30/pubmed PY - 2008/12/23/medline PY - 2007/11/30/entrez SP - 2416 EP - 26 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 33 IS - 10 N2 - Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in the suppression of a learned fear response remains to be clarified. Here, we assessed the role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2(3Y); 1.5 micromol/kg, i.v.) that blocks regulated alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor endocytosis during an initial extinction training session disrupted both the expression and recall of extinction learning. A similar impairment of extinction during training, but not recall, was observed when NMDA receptor-dependent LTD was inhibited through the selective blockade of NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat-GluR2(3Y) during fear conditioning or during a fear recall test did not effect the expression or recall of either contextual or cue-induced conditioned fear. Similarly, administration of Tat-GluR2(3Y) prior to an extinction recall test did not affect spontaneous recovery or rate of re-extinction in previously extinguished rats. These data demonstrate that AMPA receptor endocytosis does not mediate acquisition or expression of conditioned fear, but may play a role in the extinction of fear memories. Furthermore, these findings suggest that LTD may be a molecular mechanism that facilitates the selective modification of a learned association while leaving intact the ability to form a new memory. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/18046303/Disruption_of_AMPA_receptor_endocytosis_impairs_the_extinction_but_not_acquisition_of_learned_fear_ L2 - https://antibodies.cancer.gov/detail/CPTC-CALR-1 DB - PRIME DP - Unbound Medicine ER -