| First Author | Wu M | Year | 2023 |
| Journal | Neuron | PubMed ID | 37922904 |
| Mgi Jnum | J:342978 | Mgi Id | MGI:7561436 |
| Doi | 10.1016/j.neuron.2023.10.002 | Citation | Wu M, et al. (2023) Dopamine pathways mediating affective state transitions after sleep loss. Neuron |
| abstractText | 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. |
