The lateral amygdala processes the value of conditioned and unconditioned aversive stimuli

Blair, Hugh T.; Sotres-Bayón, Francisco; Moita, Marta A.; LeDoux, Joseph E.

doi:10.1016/j.neuroscience.2005.02.043

Cited by 87 publications

(84 citation statements)

References 28 publications

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“…This indicated that the fear memory was acquired and expressed to the same extent in both groups, confirming previous findings, which show that ifenprodil does not disrupt the expression of fear conditioning (Rodrigues et al, 2001;Blair et al, 2005).…”

Section: Resultssupporting

confidence: 90%

“…For example, overexpression of the NR2B subunit in mice results in enhanced learning and memory in several behavioral tasks, including fear conditioning and fear extinction (Tang et al, 1999). Further, blockade of NR2B-containing NMDARs with ifenprodil impairs synaptic plasticity in the amygdala without impairing routine neural transmission (Li et al, 1995;Weisskopf and LeDoux, 1999;Bauer et al, 2002), and ifenprodil also impairs fear acquisition without affecting its expression (Rodrigues et al, 2001;Blair et al, 2005). Our findings extend the role of NR2B-containing NMDARs in the acquisition of new learning to the acquisition of fear extinction.…”

Section: Discussionsupporting

confidence: 62%

“…In this study, we examined the contribution of NMDAR to extinction learning, focusing particularly on NMDARs that contain the NR2B subunit. Our results indicate that, similar to the acquisition of fear conditioning (Rodrigues et al, 2001;Blair et al, 2005), the acquisition of fear extinction requires the activation of NR2B-containing NMDARs, and that the lateral amygdala is an essential brain region underlying this mechanism.…”

Section: Discussionmentioning

confidence: 64%

“…In the final study, we evaluated the effects of local infusion of two doses of ifenprodil into the lateral amygdala. First, we tested the effect of an intraamygdala ifenprodil dose that has been shown to be sufficient to block the acquisition of fear conditioning (ifenprodil low: 1.0 mg/side) (Rodrigues et al, 2001;Blair et al, 2005). In a separate group of animals, we assessed the effect of a higher ifenprodil dose infusion into the lateral amygdala (ifenprodil high: 5.0 mg/side).…”

Section: Nr2b In Extinction Acquisition F Sotres-bayon Et Almentioning

confidence: 99%

“…Moreover, we used ifenprodil, an antagonist that selectively blocks the NR2B subunit of NMDARs (Williams, 2001). Unlike the NMDA antagonists used previously in studies of extinction, ifenprodil disrupts the acquisition of fear conditioning without affecting fear expression or synaptic transmission (Rodrigues et al, 2001;Bauer et al, 2002;Blair et al, 2005). Further, it is now apparent that specific NMDAR channel properties depend on their subunit composition (Cull-Candy and Leszkiewicz, 2004), and the NR2B subunit is specifically involved in synaptic plasticity (Barria and Malinow, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Sotres-Bayón

Bush

LeDoux

2007

Neuropsychopharmacol

256

207

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N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity underlying learning in a variety of brain systems. Fear extinction, which involves learning to suppress the expression of previously learned fear, appears to require NMDAR activation in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning, and it is unknown whether NR2B-containing NMDARs are required in fear extinction. Here, we assessed the effects of selective NR2B blockade with ifenprodil on fear extinction learning, and found that both systemic and intra-amygdala ifenprodil treatment, given before extinction training, impaired the initial acquisition, and subsequent retrieval of fear extinction. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only the retention, of fear extinction learning. Thus, our results support a previously not known role for NMDA-dependent plasticity in the lateral amygdala during the acquisition of fear extinction.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 64%

Section: Nr2b In Extinction Acquisition F Sotres-bayon Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Sotres-Bayón

Bush

LeDoux

2007

Neuropsychopharmacol

256

207

View full text Add to dashboard Cite

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Repeated neonatal separation stress alters the composition of neurochemically characterized interneuron subpopulations in the rodent dentate gyrus and basolateral amygdala

Seidel

Helmeke

Poeggel

et al. 2008

Developmental Neurobiology

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Emotional experience during early life has been shown to interfere with the development of excitatory synaptic networks in the prefrontal cortex, hippocampus, and the amygdala of rodents and primates. The aim of the present study was to investigate a developmental "homoeostatic synaptic plasticity" hypothesis and to test whether stress-induced changes of excitatory synaptic composition are counterbalanced by parallel changes of inhibitory synaptic networks. The impact of repeated early separation stress on the development of two GABAergic neuronal subpopulations was quantitatively analyzed in the brain of the semiprecocial rodent Octodon degus. Assuming that PARV- and CaBP-D28k-expression are negatively correlated to the level of inhibitory activity, the previously described reduced density of excitatory spine synapses in the dentate gyrus of stressed animals appears to be "amplified" by elevated GABAergic inhibition, reflected by reduced PARV- (down to 85%) and CaBP-D28k-immunoreactivity (down to 74%). In opposite direction, the previously observed elevated excitatory spine density in the CA1 region of stressed animals appears to be amplified by reduced inhibition, reflected by elevated CaPB-D28k-immunoreactivity (up to 149%). In the (baso)lateral amygdala, the previously described reduction of excitatory spine synapses appears to be "compensated" by reduced inhibitory activity, reflected by dramatically elevated PARV- (up to 395%) and CaPB-D28k-immunoreactivity (up to 327%). No significant differences were found in the central nucleus of the amygdala, the piriform, and somatosensory cortices and in the hypothalamic paraventricular nucleus. Thus during stress-evoked neuronal and synaptic reorganization, a homeostatic balance between excitation and inhibition is not maintained in all regions of the juvenile brain.

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Limbic dysregulation is associated with lowered heart rate variability and increased trait anxiety in healthy adults

Mujica‐Parodi¹,

Korgaonkar²,

Ravindranath³

et al. 2007

Human Brain Mapping

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Objectives: We tested whether dynamic interaction between limbic regions supports a control systems model of excitatory and inhibitory components of a negative feedback loop, and whether dysregulation of those dynamics might correlate with trait differences in anxiety and their cardiac characteristics among healthy adults. Experimental Design: Sixty-five subjects received fMRI scans while passively viewing angry, fearful, happy, and neutral facial stimuli. Subjects also completed a trait anxiety inventory, and were monitored using ambulatory wake ECG. The ECG data were analyzed for heart rate variability, a measure of autonomic regulation. The fMRI data were analyzed with respect to six limbic regions (bilateral amygdala, bilateral hippocampus, Brodmann Areas 9, 45) using limbic time-series cross-correlations, maximum BOLD amplitude, and BOLD amplitude at each point in the time-series. Principal Observations: Diminished coupling between limbic time-series in response to the neutral, fearful, and happy faces was associated with greater trait anxiety, greater sympathetic activation, and lowered heart rate variability. Individuals with greater levels of trait anxiety showed delayed activation of Brodmann Area 45 in response to the fearful and happy faces, and lowered Brodmann Area 45 activation with prolonged left amygdala activation in response to the neutral faces. Conclusions: The dynamics support limbic regulation as a control system, in which dysregulation, as assessed by diminished coupling between limbic time-series, is associated with increased trait anxiety and excitatory autonomic outputs. Trait-anxious individuals showed delayed inhibitory activation in response to overt-affect stimuli and diminished inhibitory activation with delayed extinction of excitatory activation in response to ambiguous-affect stimuli.

show abstract

The lateral amygdala processes the value of conditioned and unconditioned aversive stimuli

Cited by 87 publications

References 28 publications

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Repeated neonatal separation stress alters the composition of neurochemically characterized interneuron subpopulations in the rodent dentate gyrus and basolateral amygdala

Limbic dysregulation is associated with lowered heart rate variability and increased trait anxiety in healthy adults

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