Article

Cellular and oscillatory substrates of fear extinction learning

  • Nature Neuroscience volume 20, pages 16241633 (2017)
  • doi:10.1038/nn.4651
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Abstract

The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6–12 Hz oscillation and a fear-associated 3–6 Hz oscillation within the BLA. Loss of this competition increases a 3–6 Hz oscillatory signature, with BLA→medial prefrontal cortex directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

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Acknowledgements

We thank B. Roth (UNC Vector Core) and E. Callaway (Salk Institute) for reagents. We thank A. Poulopoulos and T. Papouin for discussions and critical reading of the manuscript. We thank J. Sasaki Russell and S. Viola for technical assistance. This work was supported in part by grants to L.G.R. (NIH R01 MH104589) and J.M. (NIH R01 NS102937), and by the Tufts Center for Neuroscience Research (NIH P30 NS047243). P.D. was supported by the Synapse Neurobiology Training Program (NIH T32 NS061764) and the Medical Scientist Training Program at Tufts University (NIH T32 GM008448).

Author information

Affiliations

  1. Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.

    • Patrick Davis
    • , Yosif Zaki
    • , Jamie Maguire
    •  & Leon G Reijmers
  2. Medical Scientist Training Program and Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.

    • Patrick Davis

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Contributions

P.D., J.M., and L.G.R. conceived and designed the experiments. P.D. and Y.Z. executed the experiments. P.D., Y.Z., and L.G.R. analyzed the experiments. P.D. and L.G.R. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Leon G Reijmers.

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