Neural mechanism underlying eye movement desensitization and reprocessing for post-traumatic stress disorder in mouse model

Abstract

A psychotherapeutic regimen that uses alternating bilateral sensory stimulation (ABS) has been used to treat post-traumatic stress disorder in humans. 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 non-invasive visual stimulation of 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) throughout the extinction session. 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 complex of the amygdala (BLA). The direct MD-BLA projection formed a novel feedforward inhibitory circuit that was required for the observed long-lasting suppression of fear. Together, these results reveal the neural circuit that underlies an effective strategy for sustainably attenuating traumatic memories.