Full text is available at the source.
TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine
Interaction between two brain receptors may explain how ketamine changes synapse adaptability
AI simplified
Abstract
The antidepressant action of ketamine is dependent on the receptor tyrosine kinase tropomyosin-related kinase B (TrkB) and the G protein-coupled receptor metabotropic glutamate receptor 5 (mGluR5).
- mGluR5 amplifies the signaling of brain-derived neurotrophic factor (BDNF) through TrkB, facilitating synaptic strengthening.
- BDNF activation of TrkB triggers the internalization of mGluR5, which may impair synaptic weakening.
- Ketamine enhances the interaction between TrkB and mGluR5, increasing their surface and postsynaptic levels.
- An mGluR5 positive allosteric modulator can further enhance the signaling cross-talk between TrkB and mGluR5.
- These findings suggest that the interplay between different neuromodulatory receptors could influence therapeutic outcomes.
AI simplified