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Science 319 (5866): 1104-1107

Copyright © 2008 by the American Association for the Advancement of Science

Spine-Type-Specific Recruitment of Newly Synthesized AMPA Receptors with Learning

Naoki Matsuo,*{dagger} Leon Reijmers, Mark Mayford*

Abstract: The stabilization of long-term memories requires de novo protein synthesis. How can proteins, synthesized in the soma, act on specific synapses that participate in a given memory? We studied the dynamics of newly synthesized AMPA-type glutamate receptors (AMPARs) induced with learning using transgenic mice expressing the GluR1 subunit fused to green fluorescent protein (GFP-GluR1) under control of the c-fos promoter. We found learning-associated recruitment of newly synthesized GFP-GluR1 selectively to mushroom-type spines in adult hippocampal CA1 neurons 24 hours after fear conditioning. Our results are consistent with a "synaptic tagging" model to allow activated synapses to subsequently capture newly synthesized receptor and also demonstrate a critical functional distinction in the mushroom spines with learning.

Department of Cell Biology and Institute for Childhood and Neglected Diseases, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

{dagger} Present address: Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.

* To whom correspondence should be addressed. E-mail: n-matsuo{at} (N.M.); mmayford{at} (M.M.)

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S. D. Mhatre, V. Satyasi, M. Killen, B. E. Paddock, R. D. Moir, A. J. Saunders, and D. R. Marenda (2014)
Dis. Model. Mech. 7, 373-385
   Abstract »    Full Text »    PDF »
Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model.
C.-S. Lim, E. T. Hoang, K. E. Viar, R. L. Stornetta, M. M. Scott, and J. J. Zhu (2014)
Genes & Dev. 28, 273-289
   Abstract »    Full Text »    PDF »
Dendritic Spines: The Locus of Structural and Functional Plasticity.
C. Sala and M. Segal (2014)
Physiol Rev 94, 141-188
   Abstract »    Full Text »    PDF »
Altered Structural and Functional Synaptic Plasticity with Motor Skill Learning in a Mouse Model of Fragile X Syndrome.
R. Padmashri, B. C. Reiner, A. Suresh, E. Spartz, and A. Dunaevsky (2013)
J. Neurosci. 33, 19715-19723
   Abstract »    Full Text »    PDF »
The synaptic plasticity and memory hypothesis: encoding, storage and persistence.
T. Takeuchi, A. J. Duszkiewicz, and R. G. M. Morris (2013)
Phil Trans R Soc B 369, 20130288
   Abstract »    Full Text »    PDF »
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C. J. Fontaine, C. W. Harley, and Q. Yuan (2013)
J. Neurosci. 33, 15126-15131
   Abstract »    Full Text »    PDF »
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 »
CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses.
L. M. Farmer, B. N. Le, and D. J. Nelson (2013)
J. Physiol. 591, 1001-1015
   Abstract »    Full Text »    PDF »
Central Amygdala GluA1 Facilitates Associative Learning of Opioid Reward.
Y.-Q. Cai, W. Wang, Y.-Y. Hou, Z. Zhang, J. Xie, and Z. Z. Pan (2013)
J. Neurosci. 33, 1577-1588
   Abstract »    Full Text »    PDF »
Enhanced Recruitment of Endosomal Na+/H+ Exchanger NHE6 into Dendritic Spines of Hippocampal Pyramidal Neurons during NMDA Receptor-Dependent Long-Term Potentiation.
E. C. Deane, A. E. Ilie, S. Sizdahkhani, M. Das Gupta, J. Orlowski, and R. A. McKinney (2013)
J. Neurosci. 33, 595-610
   Abstract »    Full Text »    PDF »
Functional anatomy of neural circuits regulating fear and extinction.
E. Knapska, M. Macias, M. Mikosz, A. Nowak, D. Owczarek, M. Wawrzyniak, M. Pieprzyk, I. A. Cymerman, T. Werka, M. Sheng, et al. (2012)
PNAS 109, 17093-17098
   Abstract »    Full Text »    PDF »
Elimination of Dendritic Spines with Long-Term Memory Is Specific to Active Circuits.
J. Sanders, K. Cowansage, K. Baumgartel, and M. Mayford (2012)
J. Neurosci. 32, 12570-12578
   Abstract »    Full Text »    PDF »
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K. R. Myers, G. Wang, Y. Sheng, K. K. Conger, J. E. Casanova, and J. J. Zhu (2012)
J. Neurosci. 32, 11716-11726
   Abstract »    Full Text »    PDF »
Dendritic spines: from structure to in vivo function.
N. L. Rochefort and A. Konnerth (2012)
EMBO Rep. 13, 699-708
   Abstract »    Full Text »    PDF »
CREB selectively controls learning-induced structural remodeling of neurons.
S. Middei, A. Spalloni, P. Longone, C. Pittenger, S. M. O'Mara, H. Marie, and M. Ammassari-Teule (2012)
Learn. Mem. 19, 330-336
   Abstract »    Full Text »    PDF »
Generation of a Synthetic Memory Trace.
A. R. Garner, D. C. Rowland, S. Y. Hwang, K. Baumgaertel, B. L. Roth, C. Kentros, and M. Mayford (2012)
Science 335, 1513-1516
   Abstract »    Full Text »    PDF »
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N. Takahashi, K. Kitamura, N. Matsuo, M. Mayford, M. Kano, N. Matsuki, and Y. Ikegaya (2012)
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   Abstract »    Full Text »    PDF »
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K. Radwanska, N. I. Medvedev, G. S. Pereira, O. Engmann, N. Thiede, M. F. D. Moraes, A. Villers, E. E. Irvine, N. S. Maunganidze, E. M. Pyza, et al. (2011)
PNAS 108, 18471-18475
   Abstract »    Full Text »    PDF »
Contextual learning requires synaptic AMPA receptor delivery in the hippocampus.
D. Mitsushima, K. Ishihara, A. Sano, H. W. Kessels, and T. Takahashi (2011)
PNAS 108, 12503-12508
   Abstract »    Full Text »    PDF »
Insulin receptor substrate 2 is a negative regulator of memory formation.
E. E. Irvine, L. Drinkwater, K. Radwanska, H. Al-Qassab, M. A. Smith, M. O'Brien, C. Kielar, A. I. Choudhury, S. Krauss, J. D. Cooper, et al. (2011)
Learn. Mem. 18, 375-383
   Abstract »    Full Text »    PDF »
Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: Testing the AMPA receptor hypothesis in an appetitive learning model.
W. Cui, A. Darby-King, M. T. Grimes, J. G. Howland, Y. T. Wang, J. H. McLean, and C. W. Harley (2011)
Learn. Mem. 18, 283-291
   Abstract »    Full Text »    PDF »
Input-Specific Critical Periods for Experience-Dependent Plasticity in Layer 2/3 Pyramidal Neurons.
J. A. Wen and A. L. Barth (2011)
J. Neurosci. 31, 4456-4465
   Abstract »    Full Text »    PDF »
Ras and Rap Signaling in Synaptic Plasticity and Mental Disorders.
R. L. Stornetta and J. J. Zhu (2011)
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   Abstract »    PDF »
Channelrhodopsin as a tool to investigate synaptic transmission and plasticity.
P. Schoenenberger, Y.-P. Z. Scharer, and T. G. Oertner (2011)
Exp Physiol 96, 34-39
   Abstract »    Full Text »    PDF »
Cognition Enhancement Strategies.
J. A. Bibb, M. R. Mayford, J. Z. Tsien, and C. M. Alberini (2010)
J. Neurosci. 30, 14987-14992
   Abstract »    Full Text »    PDF »
Unitary inhibitory field potentials in the CA3 region of rat hippocampus.
M. l. Bazelot, C. l. Dinocourt, I. Cohen, and R. Miles (2010)
J. Physiol. 588, 2077-2090
   Abstract »    Full Text »    PDF »
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N. F. Shanks, T. Maruo, A. N. Farina, M. H. Ellisman, and T. Nakagawa (2010)
J. Neurosci. 30, 2728-2740
   Abstract »    Full Text »    PDF »
Differential effects and rates of normal aging in cerebellum and hippocampus.
D. S. Woodruff-Pak, M. R. Foy, G. G. Akopian, K. H. Lee, J. Zach, K. P. T. Nguyen, D. M. Comalli, J. A. Kennard, A. Agelan, and R. F. Thompson (2010)
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   Abstract »    Full Text »    PDF »
Experience-Dependent, Rapid Structural Changes in Hippocampal Pyramidal Cell Spines.
T. Kitanishi, Y. Ikegaya, N. Matsuki, and M. K. Yamada (2009)
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   Abstract »    Full Text »    PDF »
Behavioral tagging is a general mechanism of long-term memory formation.
F. Ballarini, D. Moncada, M. C. Martinez, N. Alen, and H. Viola (2009)
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   Abstract »    Full Text »    PDF »
Connectivity Patterns Revealed by Mapping of Active Inputs on Dendrites of Thalamorecipient Neurons in the Auditory Cortex.
R. J. Richardson, J. A. Blundon, I. T. Bayazitov, and S. S. Zakharenko (2009)
J. Neurosci. 29, 6406-6417
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Segregated Populations of Hippocampal Principal CA1 Neurons Mediating Conditioning and Extinction of Contextual Fear.
N. C. Tronson, C. Schrick, Y. F. Guzman, K. H. Huh, D. P. Srivastava, P. Penzes, A. L. Guedea, C. Gao, and J. Radulovic (2009)
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   Abstract »    Full Text »    PDF »
Environmental Enrichment Restores Memory Functioning in Mice with Impaired IL-1 Signaling via Reinstatement of Long-Term Potentiation and Spine Size Enlargement.
I. Goshen, A. Avital, T. Kreisel, T. Licht, M. Segal, and R. Yirmiya (2009)
J. Neurosci. 29, 3395-3403
   Abstract »    Full Text »    PDF »
Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors.
Y. Shinohara, H. Hirase, M. Watanabe, M. Itakura, M. Takahashi, and R. Shigemoto (2008)
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   Abstract »    Full Text »    PDF »
Ras Signaling Mechanisms Underlying Impaired GluR1-Dependent Plasticity Associated with Fragile X Syndrome.
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »

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