The pathophysiology of depression involves multiple biological processes, including circuit dysfunction and impaired neuroplasticity, yet an integrative view linking these processes remains elusive. Here, we identify a convergent circuit for antidepressant response and plasticity modulation. We demonstrate that chemogenetic activation of the infralimbic cortex (IL) exerts rapid...
Ketamine has been established as an anesthetic agent for decades. Around the turn of the millennium initial clinical studies demonstrated that subanesthetic doses of ketamine can exert antidepressant effects in treatment-resistant depression. These findings established the concept of an effective glutamatergic antidepressant treatment and initiated a paradigm shift. For many years, intravenous...
Ketamine is the first glutamatergic agent in clinical use for major depression, but its primary target remains unclear. Further research is needed to develop more specific interventions with fewer side effects. Ketamine is a noncompetitive antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Here, we show that ketamine preferentially targets GluN2D-containing NMDA receptors on...