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. 2024 Jan 3;112(1):141-154.e8.
doi: 10.1016/j.neuron.2023.10.002. Epub 2023 Nov 2.

Dopamine pathways mediating affective state transitions after sleep loss

Mingzheng Wu  1 , Xin Zhang  2 , Sihan Feng  2 , Sara N Freda  2 , Pushpa Kumari  2 , Vasin Dumrongprechachan  3 , Yevgenia Kozorovitskiy  4
Affiliations

Dopamine pathways mediating affective state transitions after sleep loss

Mingzheng Wu et al. Neuron. .

Abstract

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.

Keywords: affective state; chemogenetics; dopamine; photometry; plasticity; sleep.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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