Ketamine blocks bursting in the lateral habenula to rapidly relieve depression

@article{Yang2018KetamineBB,
  title={Ketamine blocks bursting in the lateral habenula to rapidly relieve depression},
  author={Yan Yang and Yihui Cui and Kangning Sang and Yiyan Dong and Zheyi Ni and Shuangshuang Ma and Hailan Hu},
  journal={Nature},
  year={2018},
  volume={554},
  pages={317-322}
}
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. [] Key Result LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia.
NMDA receptor-dependent long-term depression in the lateral habenula: implications in physiology and depression
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Decoding Depression: Insights from Glial and Ketamine Regulation of Neuronal Burst Firing in Lateral Habenula.
TLDR
The latest discovery on how ketamine blocks N-methyl-D-aspartate receptor (NMDAR)-dependent burst firing of an "antireward" center in the brain, the lateral habenula (LHb), to mediate its antidepressant effects is described.
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It is conceptualized that ketamine’s effects are mediated through rapid and sustained cortical disinhibition via PV-specific NRG1 signaling, which reveals a novel neural plasticity-based mechanism for ketamine's acute and long-lasting antidepressant effects.
Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents
TLDR
In a rat model of human depression, opioid antagonists abolish the ability of ketamine to reduce the depression-like behavioral and LHb hyperactive cellular phenotypes, suggesting that interactions between these two neurotransmitter systems are necessary to achieve an antidepressant effect.
Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model
TLDR
It is suggested that ketamine represents a viable candidate for the treatment of poststroke depression but also thatketamine's lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.
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