Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition.
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.
Shaban
Hamdy
H
Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
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
D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear; D058788:GABA-B Receptor Antagonists; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D058788:GABA-B Receptor Antagonists; D020033:Protein Isoforms; D018080:Receptors, GABA-B