Extinction of cued fear memory involves a distinct form of depotentiation at cortical input synapses onto the lateral amygdala.
The amygdala is known to be a critical storage site of conditioned fear memory. Among the two major pathways to the lateral amygdala (LA), the cortical pathway is known to display a presynaptic long-term potentiation which is occluded with fear conditioning. Here we show that fear extinction results in a net depression of conditioning-induced potentiation at cortical input synapses onto the LA (C-LA synapses). Fear conditioning induced a significant potentiation of excitatory postsynaptic currents at C-LA synapses compared with naïve and unpaired controls, whereas extinction apparently reversed this potentiation. Paired-pulse low-frequency stimulation (pp-LFS) induced synaptic depression in the C-LA pathway of fear-conditioned rats, but not in naïve or unpaired controls, indicating that the pp-LFS-induced depression is specific to associative learning-induced changes (pp-LFS-induced depotentiation(ex vivo)). Importantly, extinction occluded pp-LFS-induced depotentiation(ex vivo), suggesting that extinction shares some mechanisms with the depotentiation. pp-LFS-induced depotentiation(ex vivo) required NMDA receptor (NMDAR) activity, consistent with a previous finding that blockade of amygdala NMDARs impaired fear extinction. In addition, pp-LFS-induced depotentiation(ex vivo) required activity of group II metabotropic glutamate receptors (mGluRs), known to be present at presynaptic terminals, but not AMPAR internalization, consistent with a presynaptic mechanism for pp-LFS-induced depotentiation(ex vivo). This result is in contrast with another form of ex vivo depotentiation in the thalamic pathway that requires both group I mGluR activity and AMPAR internalization. We thus suggest that extinction of conditioned fear involves a distinct form of depotentiation at C-LA synapses, which depends upon both NMDARs and group II mGluRs.
School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Ingie
I
Hong
Beomjong
B
Song
Sukwon
S
Lee
Jihye
J
Kim
Jeongyeon
J
Kim
Sukwoo
S
Choi
D000161:Acoustic Stimulation / Q000009:adverse effects; D000596:Amino Acids / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D003463:Cues; D004558:Electric Stimulation / Q000379:methods; D004705:Endocytosis / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D010455:Peptides; D014966:Xanthenes; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol