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

Shaban, Hamdy; Humeau, Yann; Herry, Cyril; Cassasus, Guillaume; Shigemoto, Ryuichi; Ciocchi, Stephane; Barbieri, Samuel; van der Putten, Herman; Kaupmann, Klemens; Bettler, Bernhard; Lüthi, Andreas (2006). Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition. Nature neuroscience, 9(8), pp. 1028-35. New York, N.Y.: Nature America 10.1038/nn1732

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
UniBE Contributor:	Shaban, Hamdy
ISSN:	1097-6256
ISBN:	16819521
Publisher:	Nature America
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:45
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1038/nn1732
PubMed ID:	16819521
Web of Science ID:	000240080300015
URI:	https://boris.unibe.ch/id/eprint/18527 (FactScience: 713)