💉 NMDA Receptor Antagonism Rapid Antidepressant Mechanism Simulator

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.