Back to Search
Start Over
A synaptic locus for TrkB signaling underlying ketamine rapid antidepressant action
- Source :
- Cell reports
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- SUMMARY Ketamine produces rapid antidepressant action in patients with major depression or treatment-resistant depression. Studies have identified brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), as necessary for the antidepressant effects and underlying ketamine-induced synaptic potentiation in the hippocampus. Here, we delete BDNF or TrkB in presynaptic CA3 or postsynaptic CA1 regions of the Schaffer collateral pathway to investigate the rapid antidepressant action of ketamine. The deletion of Bdnf in CA3 or CA1 blocks the ketamine-induced synaptic potentiation. In contrast, ablation of TrkB only in postsynaptic CA1 eliminates the ketamine-induced synaptic potentiation. We confirm BDNF-TrkB signaling in CA1 is required for ketamine’s rapid behavioral action. Moreover, ketamine application elicits dynamin1-dependent TrkB activation and downstream signaling to trigger rapid synaptic effects. Taken together, these data demonstrate a requirement for BDNF-TrkB signaling in CA1 neurons in ketamine-induced synaptic potentiation and identify a specific synaptic locus in eliciting ketamine’s rapid antidepressant effects.<br />Graphical Abstract<br />In brief Lin et al. report the essential role of BDNF signaling through postsynaptic TrkB at CA3-CA1 synapses in ketamine’s synaptic potentiation and rapid antidepressant action. These findings establish a strong correlation between TrkB-dependent potentiation at the CA1 synaptic locus and the antidepressant behavioral action of ketamine.
- Subjects :
- Dynamins
Hippocampus
Tropomyosin receptor kinase B
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Mice
Neurotrophic factors
Postsynaptic potential
medicine
Animals
Humans
Receptor, trkB
Receptor
CA1 Region, Hippocampal
Neurons
Brain-Derived Neurotrophic Factor
musculoskeletal, neural, and ocular physiology
Long-term potentiation
CA3 Region, Hippocampal
Antidepressive Agents
Endocytosis
HEK293 Cells
medicine.anatomical_structure
nervous system
Schaffer collateral
Synapses
Antidepressant
Ketamine
Neuroscience
Signal Transduction
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....8bb10d0a0f938da6741b63704f537b5e