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
Nat Neurosci. 2006-07-02; 9(8): 1028-1035
DOI: 10.1038/nn1732

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1. Nat Neurosci. 2006 Aug;9(8):1028-35. Epub 2006 Jul 2.

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

Shaban H(1), Humeau Y, Herry C, Cassasus G, Shigemoto R, Ciocchi S, Barbieri S,
van der Putten H, Kaupmann K, Bettler B, Lüthi A.

Author information:
(1)Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel,
Switzerland.

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.

DOI: 10.1038/nn1732
PMID: 16819521 [Indexed for MEDLINE]


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