Blockade of amygdala metabotropic glutamate receptor subtype 1 impairs fear extinction

Kim, Jeong-Yeon; Lee, Sung‐Hee; Park, Heewoo; Song, Beomjong; Hong, Ingie; Geum, Dongho; Shin, Kisoon; Choi, Sukwoo

doi:10.1016/j.bbrc.2007.01.125

Cited by 77 publications

(65 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NMDAR dependency of pp-LFS-induced ex vivo depotentiation fits nicely with a large body of evidence that fear extinction depends on amygdala NMDARs (33,34). Similarly, blockade of group I mGluRs in the LA has recently been shown to attenuate fear extinction (35). Our findings apparently contradict the prevailing theory of fear extinction.…”

Section: Discussionsupporting

confidence: 83%

Amygdala depotentiation and fear extinction

Kim

Lee

Park

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

234

279

View full text Add to dashboard Cite

Auditory fear memory is thought to be maintained by fear conditioning-induced potentiation of synaptic efficacy, which involves enhanced expression of surface AMPA receptor (AMPAR) at excitatory synapses in the lateral amygdala (LA). Depotentiation, reversal of conditioning-induced potentiation, has been proposed as a cellular mechanism for fear extinction; however, a direct link between depotentiation and extinction has not yet been tested. To address this issue, we applied both ex vivo and in vivo approaches to rats in which fear memory had been consolidated. A unique form of depotentiation reversed conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo. Extinction returned the enhanced T-LA synaptic efficacy observed in conditioned rats to baseline and occluded the depotentiation. Consistently, extinction reversed conditioning-induced enhancement of surface expression of AMPAR subunits in LA synaptosomal preparations. A GluR2-derived peptide that blocks regulated AMPAR endocytosis inhibited depotentiation, and microinjection of a cell-permeable form of the peptide into the LA attenuated extinction. Our results are consistent with the use of depotentiation to weaken potentiated synaptic inputs onto the LA during extinction and provide strong evidence that AMPAR removal at excitatory synapses in the LA underlies extinction.lateral amygdala ͉ fear conditioning ͉ AMPA receptor ͉ endocytosis T he cortical and thalamic input synapses onto the lateral amygdala (LA) (C-LA and T-LA synapses, respectively) carry auditory information from the auditory cortex and auditory thalamus onto the LA, respectively (1). Long-term potentiation (LTP; an in vitro model of memory) (2)-like changes in these pathways are thought to underlie both the encoding and consolidation of auditory fear memory (3-8). The results of a recent study suggest that long-term retention of conditioning-induced potentiation at excitatory synapses in the LA is a critical requirement for consolidated fear memory within the LA (7, 9). Also, LTP requiring the synaptic delivery of AMPA receptors (AMPARs) at excitatory synapses in the LA appears to be necessary for establishing consolidated fear memory (6,8,10). Conditioning-induced potentiation and auditory fear memory encoded in the LA have been shown to be consolidated within 24 h after fear conditioning (5, 7, 11). Moreover, auditory fear memory appears to be maintained in the LA across the adult lifetime of rats (12). Thus, consolidation of auditory fear memory encoded in the LA is rapid and localized, unlike hippocampus-dependent memory, which involves slow and distributed consolidation processes (13).In the present study, we tested the hypothesis that depotentiation of conditioning-induced potentiation at excitatory synapses in the LA underlies extinction of consolidated fear memory. Synaptic weights were monitored ex vivo by using whole-cell (or field potential) recordings in amygdala slices prepared from behaviortrained rats. Results Extinction of Consolidated ...

show abstract

Section: Discussionsupporting

confidence: 83%

Amygdala depotentiation and fear extinction

Kim

Lee

Park

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

234

279

View full text Add to dashboard Cite

show abstract

“…This is consistent with the current neural model of fear extinction Quirk and Mueller 2007) that involves interactions between several structures including the BLA and the mPFC. In addition to its key role in fear learning and fear expression (Maren 2001;Rodrigues et al 2004), the BLA appears necessary for the acquisition and the consolidation of extinction memory (Lin et al 2003;Herry and Mons 2004;Herry et al 2006;Kim et al 2007;Sotres-Bayon et al 2007). Activity in the mPFC is not critical for the acquisition of extinction memory but appears important for its consolidation and expression (Milad and Quirk 2002;Barrett et al 2003;Herry and Mons 2004;Hugues et al 2004Hugues et al , 2006Santini et al 2004;Burgos-Robles et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Fear extinction is also critically dependent upon the BLA. For instance, local blockade of NMDA receptors (NMDAr), metabotropic glutamate receptors, or mitogen-activated protein kinase (MAPk) activity impairs the acquisition of extinction (Herry et al 2006;Kim et al 2007;Sotres-Bayon et al 2007). Moreover, the consolidation of extinction requires activation in the BLA of the phosphoinositide-3 kinase pathway, synthesis of new protein, and the expression of immediate early genes (IEGs) (Lin et al 2003;Herry and Mons 2004).…”

mentioning

confidence: 99%

The basolateral amygdala is necessary for learning but not relearning extinction of context conditioned fear

Laurent¹,

Marchand²,

Westbrook³

2008

Learn. Mem.

View full text Add to dashboard Cite

Extinction of conditioned fear involves new learning that inhibits but does not eliminate the original fear memory. This inhibitory learning is thought to require activation of NMDA receptors (NMDAr) within the basolateral amygdala (BLA). However, once extinction has been learned, the role played by the BLA during subsequent extinction procedures remains unknown. The present study examined the role of neuronal activity and NMDAr activation in rats receiving their first or second extinction of context fear. We found that BLA infusion of DL-APV, a competitive antagonist of NMDAr, depressed fear responses at both the first and second extinction. It impaired learning extinction but spared and even facilitated relearning extinction. BLA infusion of muscimol, a GABA A agonist, produced a similar outcome, suggesting that DL-APV not only blocked NMDAr-dependent plasticity but also disrupted neuronal activity. In contrast, infusion of ifenprodil, a more selective antagonist of NMDAr containing the NR2B subunit, did not depress fear responses but impaired short-and long-term inhibition of fear at both the first and second extinction. Therefore, we suggest that relearning extinction normally requires NMDAr containing the NR2B subunit in the BLA. However, simultaneous blockade of these receptors and neuronal activity in the BLA results in compensatory learning that is able to promote long-term re-extinction. These data are consistent with a current model that attributes fear extinction to interactions between several neural substrates, including the amygdala and the medial prefrontal cortex.

show abstract

“…However, pharmacological and electrophysiological studies in rats suggest that the amygdala has an important function in the acquisition and consolidation of fear extinction. Recent studies have shown that blockade of NMDA (Sotres-Bayon et al, 2007) or glutamate (Kim et al, 2007) receptors within the basolateral amygdala complex (BLA) impaired extinction learning and that the blockade of mitogen-activated protein kinase (MAPk) activity in the basolateral nucleus entirely prevented the acquisition of extinction (Herry et al, 2006). Furthermore, several studies suggest that morphological changes in the BLA synapses after extinction training support the consolidation of extinction learning (Lin et al, 2003;Chhatwal et al, 2005Chhatwal et al, , 2006Markram et al, 2007).…”

Section: Extinctionmentioning

confidence: 99%

Changing Fear: The Neurocircuitry of Emotion Regulation

Hartley

Phelps

2009

Neuropsychopharmacol

430

346

View full text Add to dashboard Cite

The ability to alter emotional responses as circumstances change is a critical component of normal adaptive behavior and is often impaired in psychological disorders. In this review, we discuss four emotional regulation techniques that have been investigated as means to control fear: extinction, cognitive regulation, active coping, and reconsolidation. For each technique, we review what is known about the underlying neural systems, combining findings from animal models and human neuroscience. The current evidence suggests that these different means of regulating fear depend on both overlapping and distinct components of a fear circuitry.

show abstract

Blockade of amygdala metabotropic glutamate receptor subtype 1 impairs fear extinction

Cited by 77 publications

References 24 publications

Amygdala depotentiation and fear extinction

Amygdala depotentiation and fear extinction

The basolateral amygdala is necessary for learning but not relearning extinction of context conditioned fear

Changing Fear: The Neurocircuitry of Emotion Regulation

Contact Info

Product

Resources

About