A synaptic locus for TrkB signaling underlying ketamine rapid antidepressant action
Cell Reports August 1, 2021 Pei-Yi Lin, Z. Z. Ma, Melissa Mahgoub et al. 97 citations
Ketamine rapidly relieves depression by activating BDNF-TrkB signaling specifically in CA1 neurons of the hippocampus. Deleting BDNF in either CA3 or CA1, or deleting its receptor TrkB only in postsynaptic CA1, blocks ketamine-induced synaptic strengthening. Ketamine triggers dynamin1-dependent TrkB activation and downstream signaling to produce these rapid synaptic effects. The findings pinpoint a precise synaptic location—CA1 neurons—where BDNF-TrkB signaling is required for ketamine's rapid antidepressant action.