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Original Research Article
Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors

1  Laboratory for Integrative Neuroscience, Section on Behavioral Science and Genetics , National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, USA
2  Max Planck Institute for Medical Research, Germany


There is compelling evidence that L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptors containing the GluR1 subunit contribute to the molecular mechanisms associated with learning. AMPA GluR1 glutamate receptor knockout mice (KO) exhibit abnormal hippocampal and amygdala plasticity, and deficits on various assays for cognition including Pavlovian fear conditioning. Here we examined associative fear learning in mice with complete absence (KO) or partial loss (heterozygous mutant, HET) of GluR1 on multiple fear conditioning paradigms. After multi-trial delay or trace conditioning, KO displayed impaired tone and context fear recall relative to WT, whereas HET were normal. After one-trial delay conditioning, both KO and HET showed impaired tone and context recall. HET and KO showed normal nociceptive sensitivity in the hot plate and tail flick tests. These data demonstrate that the complete absence of GluR1 subunit-containing receptors prevents the formation of associative fear memories, while GluR1 haploinsufficiency is sufficient to impair one-trial fear learning. These findings support growing evidence of a major role for GluR1-containing AMPA receptors in amygdalamediated forms of learning and memory.

Keywords: glutamate, learning, GluRl, AMPA, mouse

Citation: Feyder M, Wiedholz L, Sprengel R and Holmes A (2007) Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors. Front. Behav. Neurosci. (2007) 1:4. doi:10.3389/neuro.08.004.2007

Received: 13 October 2007; paper pending published: 16 November 2007; accepted: 12 December 2007; published online: 30 December 2007.

Edited by: 
Carmen Sandi, Ecole Polytechnique Federale De Lausanne, Switzerland

Reviewed by: 
Sabrina Davis, Université Paris Sud, France
Lisa A. Conboy, Ecole Polytechnique Fédérale de Lausanne, Switzerland

Copyright: © 2007 Feyder, Wiedholz, Sprengel and Holmes. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: Andrew Holmes, Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N09, Rockville MD 20852-9411, USA. e-mail: holmesan@mail.nih.gov
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