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

NARA I. MURARO

Lovaina (el evento fue virtual, via zoom)

Seminario; Fly Club VIB KU-Leuven Center for Brain & Disease Research; 2021

VIB KU-Leuven Center for Brain & Disease Research, Lovaina, Bélgica

Circadian rhythms have been extensively studied in the fruit fly where many clock genes that interlock through negative feedback loops and generate daily oscillations have been described. Clock genes are expressed in approximately 150 clock neurons in the Drosophila brain. Among them, the pigment dispersing factor (PDF)-expressing lateral ventral neurons (LNvs) have been found to play crucial roles as the central pacemaker (the small-LNvs) and as arousal neurons (the large-LNvs). Still, little is known about how the electrical properties of Drosophila clock neurons are specified, and what mechanisms allow them to change their firing rate on a daily basis. We have performed a behavioral genetic screen through the downregulation of candidate voltage-gated ion channels using RNA-interference (RNAi) specifically in LNvs. Among the positive hits we focused our attention on the hyperpolarization-activated cation current Ih. In mammalian neurons, this channel in involved in complex neuronal behaviors such as bursting, the same firing pattern that LNvs present. I will show that Ih is important for the behaviors that LNvs command: circadian rhythms and sleep. Moreover, using whole-cell patch clamp electrophysiology in ex vivo Drosophila brains, we found that Ih is necessary to achieve the high frequency bursting firing pattern of LNvs. Since bursting firing has been associated to neuropeptide release, we hypothesized that Ih would be important for PDF-mediated communication. This is indeed the case; we found that downregulation of Ih affects PDF levels and structural plasticity of sLNvs dorsal projections.