TY - JOUR
T1 - Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition
AU - Shaban, Hamdy
AU - Humeau, Yann
AU - Herry, Cyril
AU - Cassasus, Guillaume
AU - Shigemoto, Ryuichi
AU - Ciocchi, Stephane
AU - Barbieri, Samuel
AU - Van Der Putten, Herman
AU - Kaupmann, Klemens
AU - Bettler, Bernhard
AU - Lüthi, Andreas
PY - 2006/8/1
Y1 - 2006/8/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nn1732
DO - 10.1038/nn1732
M3 - Article
C2 - 16819521
AN - SCOPUS:33747610450
VL - 9
SP - 1028
EP - 1035
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 8
ER -