2023-11-02 ノースウェスタン大学
◆急性睡眠不足の期間中、ドーパミンの放出が増加し、シナプス可塑性も高まり、次の数日間、元気な気分を維持するために脳を再配線します。
◆これらの新しい発見は、気分の変遷をよりよく理解するのに役立つだけでなく、ケタミンのような急速な効果のある抗うつ薬の働きを理解し、新しい抗うつ薬の未知のターゲットを特定するのにも役立つ可能性があります。
<関連情報>
- https://news.northwestern.edu/stories/2023/11/one-sleepless-night-can-rapidly-reverse-depression-for-several-days/
- https://www.sciencedirect.com/science/article/abs/pii/S0896627323007584
睡眠喪失後の情動状態遷移を媒介するドーパミン経路 Dopamine pathways mediating affective state transitions after sleep loss
Mingzheng Wu, Xin Zhang, Sihan Feng, Sara N. Freda, Pushpa Kumari, Vasin Dumrongprechachan, Yevgenia Kozorovitskiy
Neuron Published: November 2, 2023
DOI:https://doi.org/10.1016/j.neuron.2023.10.002
Summary
The pathophysiology of affective disorders—particularly circuit-level mechanisms underlying bidirectional, periodic affective state transitions—remains poorly understood. In patients, disruptions of sleep and circadian rhythm can trigger transitions to manic episodes, whereas depressive states are reversed. Here, we introduce a hybrid automated sleep deprivation platform to induce transitions of affective states in mice. Acute sleep loss causes mixed behavioral states, featuring hyperactivity, elevated social and sexual behaviors, and diminished depressive-like behaviors, where transitions depend on dopamine (DA). Using DA sensor photometry and projection-targeted chemogenetics, we reveal that elevated DA release in specific brain regions mediates distinct behavioral changes in affective state transitions. Acute sleep loss induces DA-dependent enhancement in dendritic spine density and uncaging-evoked dendritic spinogenesis in the medial prefrontal cortex, whereas optically mediated disassembly of enhanced plasticity reverses the antidepressant effects of sleep deprivation on learned helplessness. These findings demonstrate that brain-wide dopaminergic pathways control sleep-loss-induced polymodal affective state transitions.
Graphical abstract
