Sleep or arousal? The role of dopamine on the large lateral clock neurons

CHARLOTTE HELFRICH-FÖRSTER; FLORENCIA FERNANDEZ-CHIAPPE; CHRISTIANE HERMANN-LUIBL; N REINHARD; A PETERANDERL; M HIEKE; M SELCHO; O SHAFER; NARA I MURARO

Ashburn

Congreso; Sleep in Drosophila; 2019

HHMI Janelia Research Campus

The large lateral clock neurons (l-LNvs) are conspicuous clock neurons that appear to affect arousal and sleep. They express many receptors including activating (DopR1 and DopR2) and inhibiting (D2R) dopamine receptors and they respond dopamine by increasing cAMP levels. Furthermore, the l-LNvs are directly light sensitive and promote arousal and activity in response to light, especially in the morning. Light appears to modulate the responses of the l-LNvs to dopamine by upregulating the inhibitory dopamine receptor D2R, leading to reduced responses to dopamine during the day. This mechanism was proposed to contribute to sleep stability, e.g. during the siesta. Despite the strong responses of the l-LNvs to dopamine and their proposed role in controlling arousal and sleep, it has not been shown how dopamine signalling to the l-LNvsaffects sleep, especially not whether the activating dopamine receptors decrease sleep (increase wakefulness). Here, we downregulated the activating D1-like dopamine receptors DopR1, DopR2 specifically in the l-LNvs and studied the consequences on cAMP responses in the l-LNvs and on sleep. As expected, we found that this downregulation weakens cAMP responses to dopamine in the l-LNvs confirming that dopamine signals via DopR1 (and to a lesser extent viaDopR2) receptors. However, unexpectedly, the downregulation of DopR1 receptors slightly decreased day-sleep instead of promoting it, suggesting that dopamine signalling via DopR1 usually increases day sleep. This effect was most pronounced, when the flies were already in an aroused state. These results contradict the proposed wakefulness-promoting role of dopamine signalling to the l-LNvs.