Neural circuits underlying a psychotherapeutic regimen for fear disorders

Nature. 2019 Feb;566(7744):339-343. doi: 10.1038/s41586-019-0931-y. Epub 2019 Feb 13.

Abstract

A psychotherapeutic regimen that uses alternating bilateral sensory stimulation (ABS) has been used to treat post-traumatic stress disorder. However, the neural basis that underlies the long-lasting effect of this treatment-described as eye movement desensitization and reprocessing-has not been identified. Here we describe a neuronal pathway driven by the superior colliculus (SC) that mediates persistent attenuation of fear. We successfully induced a lasting reduction in fear in mice by pairing visual ABS with conditioned stimuli during fear extinction. Among the types of visual stimulation tested, ABS provided the strongest fear-reducing effect and yielded sustained increases in the activities of the SC and mediodorsal thalamus (MD). Optogenetic manipulation revealed that the SC-MD circuit was necessary and sufficient to prevent the return of fear. ABS suppressed the activity of fear-encoding cells and stabilized inhibitory neurotransmission in the basolateral amygdala through a feedforward inhibitory circuit from the MD. Together, these results reveal the neural circuit that underlies an effective strategy for sustainably attenuating traumatic memories.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / physiopathology
  • Anxiety / psychology*
  • Anxiety / therapy*
  • Basolateral Nuclear Complex / cytology
  • Basolateral Nuclear Complex / physiology
  • Conditioning, Classical / physiology
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Fear / psychology*
  • Feedback, Physiological
  • Male
  • Mediodorsal Thalamic Nucleus / cytology
  • Mediodorsal Thalamic Nucleus / physiology
  • Mice
  • Neural Inhibition
  • Neural Pathways / physiology*
  • Optogenetics
  • Photic Stimulation
  • Stress Disorders, Post-Traumatic
  • Superior Colliculi / cytology*
  • Superior Colliculi / physiology*
  • Time Factors