2025-05-21 浙江大学(ZJU)
<関連情報>
- https://www.zju.edu.cn/english/2025/0521/c19573a3053799/page.psp
- https://www.cell.com/cell/abstract/S0092-8674(25)00411-8
側手綱核のニューロン-アストロサイト結合が抑うつ様行動を媒介する Neuron-astrocyte coupling in lateral habenula mediates depressive-like behaviors
Qianqian Xin ∙ Junying Wang ∙ Jinkun Zheng ∙ … ∙ Xiao-Ming Li ∙ Huan Ma ∙ Hailan Hu (胡海岚)
Cell Published:April 24, 2025
DOI:https://doi.org/10.1016/j.cell.2025.04.010
Highlights
- Stress induces rapid astrocytic calcium and biphasic neuronal response in LHb
- LHb-neuron-induced phasic NE release from LC activates LHb astrocytes
- LHb astrocyte activation drives second-phase LHb neuronal response and NE release
- NET inhibitors block phasic NE and LHb-astrocytic calcium, preventing depression
Summary
The lateral habenula (LHb) neurons and astrocytes have been strongly implicated in depression etiology, but it was not clear how the two dynamically interact during depression onset. Here, using multi-brain-region calcium photometry recording in freely moving mice, we discover that stress induces a most rapid astrocytic calcium rise and a bimodal neuronal response in the LHb. LHb astrocytic calcium requires the α1A-adrenergic receptor and depends on a recurrent neural network between the LHb and locus coeruleus (LC). Through the gliotransmitter glutamate and ATP/adenosine, LHb astrocytes mediate the second-wave LHb neuronal activation and norepinephrine (NE) release. Activation or inhibition of LHb astrocytic calcium signaling facilitates or prevents stress-induced depressive-like behaviors, respectively. These results identify a stress-induced positive feedback loop in the LHb-LC axis, with astrocytes being a critical signaling relay. The identification of this prominent neuron-glia interaction may shed light on stress management and depression prevention.
