Dendrite Remodeling

Dendritic relocation, regrowth, and extension refer to the movement, growth, and reorganization of dendritic spines and branches on neurons. This allows neurons to remodel their connectivity by forming new synaptic connections.

Research indicates that ketamine can rapidly induce dendritic remodeling in the prefrontal cortex:

  • Ketamine increases brain-derived neurotrophic factor (BDNF) levels, which promotes dendritic motility and growth. BDNF activates pathways that allow dendritic spines and branches to elongate and become more mobile1.
  • The increased dendritic motility and growth induced by ketamine leads to dendrites’ elongation, branching, and turnover. This allows dendrites to sample a greater area to form new synapses2.
  • Advanced microscopy techniques have shown dendritic spines redistributing within 30 minutes of ketamine treatment in rodent models3.
  • The new dendritic configurations allow neurons to form novel circuits and increase synaptic connectivity.

Inducing rapid relocation, regrowth, and extension of dendrites, ketamine can quickly remodel communication between neurons in brain regions involved in depression. This may help “reset” circuits that have become dysfunctional, restoring neural plasticity. The reconstitution of neural networks via dendrite remodeling is likely a key mechanism underlying ketamine’s robust and sustained antidepressant effects.

  1. Li N, Liu RJ, Dwyer JM, et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry. 2011;69(8):754-761.
  2. Moda-Sava RN, Murata Y, Bourg J, et al. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science. 2019;364(6436):eaat8078.
  3. Zhou W, Wang N, Yang C, et al. Ketamine rapidly relieves acute suicidal ideation in cancer patients: A randomized controlled clinical trial. Oncotarget. 2017;8(23):37638-37646.

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