Ketamine Docks Inside the Open NMDA Channel Pore
Placeholder: ketamine plugs the NMDA channel as a use-dependent open-channel blocker.
- PCP site: Binding site (Placeholder short note)
- Open: Channel state req. (Placeholder short note)
- ~0.5 µM: Affinity (Placeholder short note)
- Seconds: Onset (Placeholder short note)
Use-dependent channel block
Placeholder: ketamine enters only when the NMDA channel is already open and active.
Inhibitory GABAergic Interneurons Lose Their Drive
Placeholder: NMDA blockade preferentially quiets fast-spiking inhibitory interneurons.
- PV+ interneuron: Cell type (Placeholder short note)
- High: NMDA sensitivity (Placeholder short note)
- ~60%: Firing rate drop (Placeholder short note)
- Disinhibition: Effect (Placeholder short note)
Selective interneuron vulnerability
Placeholder: interneurons rely more heavily on tonic NMDA current than pyramidal cells.
Disinhibition Unleashes a Burst of Glutamate Release
Placeholder: with inhibition removed, pyramidal neurons release a glutamate surge.
- ~3-5×: Glutamate rise (Placeholder short note)
- Pyramidal cells: Source (Placeholder short note)
- Prefrontal cortex: Region (Placeholder short note)
- Minutes: Duration (Placeholder short note)
Cortical glutamate burst
Placeholder: microdialysis studies show a transient prefrontal glutamate spike.
AMPA Receptors Fire in a Rapid Excitatory Burst
Placeholder: the glutamate surge drives strong AMPA receptor activation on dendrites.
- AMPA: Receptor (Placeholder short note)
- Fast, ms-scale: Kinetics (Placeholder short note)
- AMPA-dependent: Dependency (Placeholder short note)
- NBQX (in vivo): Blocked by (Placeholder short note)
AMPA-dependent excitatory burst
Placeholder: AMPA throughput is required for the rapid antidepressant response.
This Burst Is the Ignition Point for the Plasticity Cascade
Placeholder: the AMPA burst is upstream of BDNF release and synaptogenesis, not that outcome itself.
- BDNF release: Next step (Placeholder short note)
- mTOR, synaptogenesis: Downstream (Placeholder short note)
- Receptor-level only: This page scope (Placeholder short note)
- Neuroplasticity sim: See also (Placeholder short note)
Handoff to the plasticity cascade
Placeholder: this simulator stops here, right before BDNF-driven synaptogenesis begins.
Placeholder: full downstream neuroplasticity cascade is covered in a separate simulator.