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Synaptic correlates of fear extinction in the amygdala

Abstract

Anxiety disorders such as post-traumatic stress are characterized by an impaired ability to learn that cues previously associated with danger no longer represent a threat. However, the mechanisms underlying fear extinction remain unclear. We found that fear extinction in rats was associated with increased levels of synaptic inhibition in fear output neurons of the central amygdala (CEA). This increased inhibition resulted from a potentiation of fear input synapses to GABAergic intercalated amygdala neurons that project to the CEA. Enhancement of inputs to intercalated cells required prefrontal activity during extinction training and involved an increased transmitter release probability coupled to an altered expression profile of ionotropic glutamate receptors. Overall, our results suggest that intercalated cells constitute a promising target for pharmacological treatment of anxiety disorders.

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Figure 1: Increased inhibition of CEm neurons in extinction and conditioned inhibition.
Figure 2: Group-related differences in CEm EPSP slopes and orthodromic spiking in response to BLA stimulation.
Figure 3: Increased recruitment of CEl neurons by BLA inputs in conditioned inhibition.
Figure 4: Enhanced efficacy of BLA synapses onto ITC cells in extinction.
Figure 5: Mechanisms underlying increased BLA responsiveness of ITC cells in extinction.
Figure 6: Infralimbic (IL) inactivation blocks extinction-related changes in the efficacy of BLA synapses onto ITC cells.

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Acknowledgements

This work was supported by National Institute of Mental Health grant RO1 MH083710 to D.P.

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Contributions

T.A. and C.T.U. performed all of the electrophysiological experiments and most of the analyses on ITC and CEA cells, respectively. T.A. performed the behavioral training and C.T.U. scored the behavior. D.P. designed the experiments, wrote the paper and contributed to data analysis.

Corresponding author

Correspondence to Denis Paré.

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The authors declare no competing financial interests.

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Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Tables 1–14 and Supplementary Results (PDF 512 kb)

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Amano, T., Unal, C. & Paré, D. Synaptic correlates of fear extinction in the amygdala. Nat Neurosci 13, 489–494 (2010). https://doi.org/10.1038/nn.2499

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