Signaling pathways underlying the rapid antidepressant actions of ketamine

► Clinical studies demonstrate that ketamine produces a rapid antidepressant response. ► Ketamine rapidly increases synaptogenesis in rodent prefrontal cortex. ► Ketamine-induction of synaptogenesis requires mTOR signaling. ► Ketamine rapidly reverses synaptic loss caused by stress and depression. ► Ketamine results in a functional reconnection of neurons.