Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition

Hamdy Shaban, Yann Humeau, Cyril Herry, Guillaume Cassasus, Ryuichi Shigemoto, Stephane Ciocchi, Samuel Barbieri, Herman Van Der Putten, Klemens Kaupmann, Bernhard Bettler, Andreas Lüthi

Research output: Contribution to journalArticlepeer-review

148 Citations (Scopus)

Abstract

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 GABA B(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 GABA B(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.

Original languageEnglish
Pages (from-to)1028-1035
Number of pages8
JournalNature Neuroscience
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 1 2006

ASJC Scopus subject areas

  • Neuroscience(all)

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