A complex ensemble of neuromodulatory receptors orchestrates the many forms of synaptic plasticity that drive behavioral state changes, but an understanding of how such receptors functionally interact is limited. Here, we find that the antidepressant action of ketamine is dependent on both the receptor tyrosine kinase, tropomyosin-related kinase B (TrkB), and the G protein-coupled receptor,...
Depression is driven by dysfunction in discrete neural circuits, but a deeper understanding of the underlying molecular and synaptic mechanisms is needed to guide the development of therapeutics. Here, we decipher the mechanisms of action of the fast-acting antidepressant ketamine to enable the identification of G protein-coupled receptor (GPCR) antidepressant targets. We find that the...