4.7 Article

Cellular and oscillatory substrates of fear extinction learning

Journal

NATURE NEUROSCIENCE
Volume 20, Issue 11, Pages 1624-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4651

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Funding

  1. Tufts Center for Neuroscience Research [NIH P30 NS047243]
  2. Synapse Neurobiology Training Program [NIH T32 NS061764]
  3. Medical Scientist Training Program at Tufts University [NIH T32 GM008448]
  4. [NIH R01 MH104589]
  5. [NIH R01 NS102937]

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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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