The Ih channel shapes circadian rhythms and sleep through the control of neuronal bursting frequency

LIA FRENKEL; MARIA FERNANDA CERIANI; CARINA C. COLQUE; ANA RICCIUTI; NARA I MURARO; FLORENCIA FERNANDEZ-CHIAPPE

Ashburn, Virginia

Congreso; Sleep in Drosophila; 2019

HHMI Janelia Research Campus

Sleep is highly influenced by the circadian clock. However, there is still a lot to learn concerning how the electrical properties of Drosophila clock neurons are specified, what mechanisms allow them to change their firing rate on a daily basis, and how this impacts on sleep behavior. To shed light on these questions, we have performed a behavioral genetic screen through the downregulation of candidate ion channels using RNA-interference on the pigment dispersing factor (PDF)-expressing lateral ventral neurons (LNvs). Among the positive hits of our screen we focused our attention on the hyperpolarization-activated cation current Ih. In mammalian neurons, this channel is involved in complex neuronal behaviors such as bursting, the same firing pattern that large-LNvs display. Using whole-cell patch clamp electrophysiology we demonstrate that small-LNvs are bursting neurons, and that Ih is necessary to achieve the normally high frequency bursting firing pattern of both types of LNvs. Since firing in bursts has been associated to neuropeptide release, we hypothesized that Ih would be important for PDF mediated communication. This is indeed the case; we prove that Ih is fundamental for the regulation of PDF levels and for the structural remodeling of the small-LNv dorsal projections. Finally, we found that downregulation of Ih not only affects circadian behavior, but it also increases sleep. Interestingly, our results demonstrate that Ih influences sleep consolidation in different ways depending on the neuronal cluster where the genetic manipulation is performed.