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

Full 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 GABA(B) receptor subtype, GABA(B(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 GABA(B(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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Author information

Author/s: Shaban, Hamdy (H); Humeau, Yann (Y); Herry, Cyril (C); Cassasus, Guillaume (G); Shigemoto, Ryuichi (R); Ciocchi, Stephane (S); Barbieri, Samuel (S); van der Putten, Herman (H); Kaupmann, Klemens (K); Bettler, Bernhard (B); Lüthi, Andreas (A);

Affiliation: Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Nature neuroscience (Nat Neurosci), published in United States. (Language: eng)

Reference: 2006-Aug; vol 9 (issue 8) : pp 1028-35

Dates: Created 2006/07/27; Completed 2006/09/27; Revised 2006/11/15;

PMID: 16819521, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amygdala - cytology; physiology
Animals
Association Learning - physiology
Behavior, Animal - physiology
Conditioning, Classical - physiology
Fear
Long-Term Potentiation - physiology
Male
Mice

Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Neuronal Plasticity - physiology
Neurons - metabolism; ultrastructure
Patch-Clamp Techniques
Protein Isoforms - metabolism
Receptors, GABA-B - antagonists & inhibitors; genetics; metabolism
Synaptic Transmission - physiology

Associated Chemicals: Protein Isoforms (0) ; Receptors, GABA-B (0)

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