TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.
Science advances May 1, 2026 Anisul Arefin, Jihye Kim, Manas Pratim Chakraborty et al. 1 citation
Ketamine's antidepressant effects depend on the interplay between two types of neuromodulatory receptors: TrkB and mGluR5. mGluR5 amplifies BDNF-driven signaling through TrkB, enabling synaptic potentiation, while BDNF activation of TrkB drives mGluR5 endocytosis, impairing synaptic depression. Ketamine enhances these interactions by increasing surface and postsynaptic levels of TrkB. An mGluR5 positive allosteric modulator can further boost both modes of cross-talk and enhance ketamine's effects, revealing that receptor-receptor interplay can drive therapeutic action.