Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells.
Neuron September 25, 2024 Ming Li, Xue-Ke Yang, Jian Yang et al. 30 citations
Traumatic memories from social defeat stress in mice are stored in engram cells of the basolateral amygdala (BLA). A single low dose of ketamine given during, but not after, a brief re-exposure to the trauma context reduces social avoidance behavior. This effect lowers both the activity and number of reactivated BLA engram cells. Dopamine projections from the ventral tegmental area to the BLA, acting through dopamine D2 receptors, can mimic or block the therapeutic effect. Single-cell RNA sequencing shows that re-exposure with ketamine alters memory-related pathways in the BLA. The findings suggest a mechanism for how ketamine may alleviate PTSD symptoms and point to potential treatments for trauma-related disorders.