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bioRxiv · 10.1101/2022.01.30.478401

Orexin action on the dopaminergic system modulates theta during REM sleep and wakefulness

Bandarabadi, M.·Li, S.·Tafti, M.·Colombo, G.·Becchetti, A.·Vassalli, A.
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Abstract

Both dopaminergic (DA) and orexinergic (OX) systems establish brain-wide neuromodulatory circuits that profoundly influence brain states and behavioral outputs. To unravel their interactions, we inactivated OX-to-DA neurotransmission by selective disruption of HcrtR1/OxR1, or HcrtR2/OxR2, or both receptors, in DA neurons. Chronic loss of OXR2 in DA neurons (OxR2Dat-CKO mice) dramatically increased electrocorticographic (EcoG) theta rhythms in wakefulness and REM sleep. Episode duration and total times spent in active wakefulness and REMS were prolonged, and theta/fast-gamma wave coupling was enhanced in both states. Increased theta in OxR2DatCKO mice baseline wake was accompanied by diminished infra-theta and increased fast-gamma activities, i.e. the mice exhibited signs of constitutive electrocortical hyperarousal, albeit uncoupled with locomotor activity. These effects were not seen in OxR1-ablated dopaminergic mutants, which tended to show opposite phenotypes, resembling those caused by the loss of both receptors. Our data establish a clear, genetically-defined link between monosynaptic orexin-to-dopaminergic connectivity and the power of theta oscillations, with a differential role of OXR2 in cross-frequency wave coupling and attentional processes.

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Bandarabadi, M., Li, S., Tafti, M., Colombo, G., Becchetti, A., Vassalli, A.. 2022-01-31. Orexin action on the dopaminergic system modulates theta during REM sleep and wakefulness. https://doi.org/10.1101/2022.01.30.478401

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