Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 330 (6007): 1108-1112

Copyright © 2010 by the American Association for the Advancement of Science

Calcium-Permeable AMPA Receptor Dynamics Mediate Fear Memory Erasure

Roger L. Clem, and Richard L. Huganir*

Abstract: Traumatic fear memories can be inhibited by behavioral therapy for humans, or by extinction training in rodent models, but are prone to recur. Under some conditions, however, these treatments generate a permanent effect on behavior, which suggests that emotional memory erasure has occurred. The neural basis for such disparate outcomes is unknown. We found that a central component of extinction-induced erasure is the synaptic removal of calcium-permeable {alpha}-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in the lateral amygdala. A transient up-regulation of this form of plasticity, which involves phosphorylation of the glutamate receptor 1 subunit of the AMPA receptor, defines a temporal window in which fear memory can be degraded by behavioral experience. These results reveal a molecular mechanism for fear erasure and the relative instability of recent memory.

Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

* To whom correspondence should be addressed. E-mail: rhuganir{at}jhmi.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
AMPA receptor exchange underlies transient memory destabilization on retrieval.
I. Hong, J. Kim, J. Kim, S. Lee, H.-G. Ko, K. Nader, B.-K. Kaang, R. W. Tsien, and S. Choi (2013)
PNAS 110, 8218-8223
   Abstract »    Full Text »    PDF »
Cocaine-Evoked Synaptic Plasticity of Excitatory Transmission in the Ventral Tegmental Area.
C. Luscher (2013)
Cold Spring Harb Perspect Med 3, a012013
   Abstract »    Full Text »    PDF »
Fear Extinction Induces mGluR5-Mediated Synaptic and Intrinsic Plasticity in Infralimbic Neurons.
M. T. Sepulveda-Orengo, A. V. Lopez, O. Soler-Cedeno, and J. T. Porter (2013)
J. Neurosci. 33, 7184-7193
   Abstract »    Full Text »    PDF »
Activation of BDNF signaling prevents the return of fear in female mice.
D. Baker-Andresen, C. R. Flavell, X. Li, and T. W. Bredy (2013)
Learn. Mem. 20, 237-240
   Abstract »    Full Text »    PDF »
Switching off LTP: mGlu and NMDA Receptor-Dependent Novelty Exploration-Induced Depotentiation in the Rat Hippocampus.
Y. Qi, N.-W. Hu, and M. J. Rowan (2013)
Cereb Cortex 23, 932-939
   Abstract »    Full Text »    PDF »
Learning and reconsolidation implicate different synaptic mechanisms.
Y. Li, E. G. Meloni, W. A. Carlezon Jr., M. R. Milad, R. K. Pitman, K. Nader, and V. Y. Bolshakov (2013)
PNAS 110, 4798-4803
   Abstract »    Full Text »    PDF »
Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits.
J. M. Stafford, D. K. Maughan, E. C. Ilioi, and K. M. Lattal (2013)
Learn. Mem. 20, 156-163
   Abstract »    Full Text »    PDF »
Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening.
W. C. Oh, T. C. Hill, and K. Zito (2013)
PNAS 110, E305-E312
   Abstract »    Full Text »    PDF »
p300/CBP-Associated Factor Selectively Regulates the Extinction of Conditioned Fear.
W. Wei, C. M. Coelho, X. Li, R. Marek, S. Yan, S. Anderson, D. Meyers, C. Mukherjee, G. Sbardella, S. Castellano, et al. (2012)
J. Neurosci. 32, 11930-11941
   Abstract »    Full Text »    PDF »
The timing of multiple retrieval events can alter GluR1 phosphorylation and the requirement for protein synthesis in fear memory reconsolidation.
T. J. Jarome, J. L. Kwapis, C. T. Werner, R. G. Parsons, G. M. Gafford, and F. J. Helmstetter (2012)
Learn. Mem. 19, 300-306
   Abstract »    Full Text »    PDF »
Trace fear conditioning enhances synaptic and intrinsic plasticity in rat hippocampus.
C. Song, J. A. Detert, M. Sehgal, and J. R. Moyer Jr. (2012)
J Neurophysiol 107, 3397-3408
   Abstract »    Full Text »    PDF »
Taming the Amygdala: An EEG Analysis of Exposure Therapy for the Traumatized.
M. Harper (2012)
Traumatology 18, 61-74
   Abstract »    PDF »
A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse.
Y.-X. Xue, Y.-X. Luo, P. Wu, H.-S. Shi, L.-F. Xue, C. Chen, W.-L. Zhu, Z.-B. Ding, Y.-p. Bao, J. Shi, et al. (2012)
Science 336, 241-245
   Abstract »    Full Text »    PDF »
Calcium Signaling in Dendritic Spines.
M. J. Higley and B. L. Sabatini (2012)
Cold Spring Harb Perspect Biol 4, a005686
   Abstract »    Full Text »    PDF »
Ca2+ permeable AMPA receptors switch allegiances: mechanisms and consequences.
S. J. Liu and I. Savtchouk (2012)
J. Physiol. 590, 13-20
   Abstract »    Full Text »    PDF »
The Neurobiology of Fear Memory Reconsolidation and Psychoanalytic Theory.
J. M. Gorman and S. P. Roose (2011)
J Am Psychoanal Assoc 59, 1201-1220
   Abstract »    PDF »
NMDA Receptor Signaling in Oligodendrocyte Progenitors Is Not Required for Oligodendrogenesis and Myelination.
L. M. De Biase, S. H. Kang, E. G. Baxi, M. Fukaya, M. L. Pucak, M. Mishina, P. A. Calabresi, and D. E. Bergles (2011)
J. Neurosci. 31, 12650-12662
   Abstract »    Full Text »    PDF »
Enhanced synaptic plasticity in mice with phosphomimetic mutation of the GluA1 AMPA receptor.
Y. Makino, R. C. Johnson, Y. Yu, K. Takamiya, and R. L. Huganir (2011)
PNAS 108, 8450-8455
   Abstract »    Full Text »    PDF »
Disrupting reconsolidation: Pharmacological and behavioral manipulations.
M. Soeter and M. Kindt (2011)
Learn. Mem. 18, 357-366
   Abstract »    Full Text »    PDF »
The Activity-Regulated Cytoskeletal-Associated Protein (Arc/Arg3.1) Is Required for Reconsolidation of a Pavlovian Fear Memory.
S. A. Maddox and G. E. Schafe (2011)
J. Neurosci. 31, 7073-7082
   Abstract »    Full Text »    PDF »
Specific mechanism of use-dependent channel block of calcium-permeable AMPA receptors provides activity-dependent inhibition of glutamatergic neurotransmission.
A. V. Zaitsev, K. K. Kim, I. M. Fedorova, N. A. Dorofeeva, L. G. Magazanik, and D. B. Tikhonov (2011)
J. Physiol. 589, 1587-1601
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882