Nature Neuroscience 9, 1028 - 1035 (2006)
Published online: 2 July 2006; | doi:10.1038/nn1732
Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibitionHamdy Shaban1, Yann Humeau1, 2, Cyril Herry1, Guillaume Cassasus1, Ryuichi Shigemoto3, Stephane Ciocchi1, Samuel Barbieri4, Herman van der Putten5, Klemens Kaupmann5, Bernhard Bettler4 &
Andreas Lüthi11
Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland. 2
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7168, F-67084 Strasbourg, France. 3
Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, CREST, Japan Science and Technology Corporation, Kawaguchi, Japan. 4
Pharmazentrum, Department of Clinical-Biological Sciences, University of Basel, CH-4056 Basel, Switzerland. 5
Novartis Institutes for Biomedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
Correspondence should be addressed to Andreas Lüthi andreas.luthi@fmi.ch Pavlovian fear conditioning, a simple form of associative learning, is thought to involve the induction of associative, NMDA receptor–dependent long-term potentiation (LTP) in the lateral amygdala. Using a combined genetic and electrophysiological approach, we show here that lack of a specific GABAB receptor subtype, GABAB(1a,2), unmasks a nonassociative, NMDA receptor–independent form of presynaptic LTP at cortico-amygdala afferents. Moreover, the level of presynaptic GABAB(1a,2) receptor activation, and hence the balance between associative and nonassociative forms of LTP, can be dynamically modulated by local inhibitory activity. At the behavioral level, genetic loss of GABAB(1a) results in a generalization of conditioned fear to nonconditioned stimuli. Our findings indicate that presynaptic inhibition through GABAB(1a,2) receptors serves as an activity-dependent constraint on the induction of homosynaptic plasticity, which may be important to prevent the generalization of conditioned fear.
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