Decoding Depression: Insights from Glial and Ketamine Regulation of Neuronal Burst Firing in Lateral Habenula.
Yihui Cui, Yan Yang, Yiyan Dong, Hailan Hu
Cold Spring Harbor Symposia on Quantitative Biology 2018 preprint DOI: 10.1101/sqb.2018.83.036871 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Intervention | Ketamine |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Key points | The authors report that ketamine blocks NMDAR-dependent burst firing of the lateral habenula, which they describe as an "antireward" center, and propose this as the mechanism behind its rapid antidepressant effects. They further propose a glia-neuron interface mechanism to explain enhanced lateral habenula bursting in depression, suggesting new molecular targets for treating major depression. |
Abstract
The rapid antidepressant effect of ketamine is arguably one of the most significant advances in the mental health field in the last half century. However, its mechanism of action has remained elusive. Here, we describe our 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. We also discuss a novel structure-function mechanism at the glia-neuron interface to account for the enhanced LHb bursting during depression. These results reveal new molecular targets for the therapeutic intervention of major depression.
Citations in the library
Cited by 3
- Serum inflammatory cytokines in the progression of depression. Frontiers in Immunology 2026
- NMDA receptors are not necessary for burst firing of lateral habenula neurons in mice. Frontiers in Psychiatry 2026
- The N-methyl-d-aspartate receptor hypothesis of ketamine's antidepressant action: evidence and controversies. Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 29, 2024
Cites 5
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 23, 2012
- Convergent Mechanisms Underlying Rapid Antidepressant Action. CNS Drugs March 2018