Circadian control of output in Drosophila.

CERIANI, MF

Puebla

Congreso; III World Conference on Chronobiology; 2011

Circadian rhythms regulate physiology and behavior through the action of self-sustained transcriptional feedback loops of clock genes. In Drosophila, over 150 neurons in the fly brain are implicated in the circadian regulation of rest-activity cycles, but a small subset -so-called small ventral lateral neurons (sLNvs)- are clearly crucial. Preservation of molecular oscillations within the sLNvs is essential to command rhythmic behavior under free running conditions. The sLNvs transmit this ¨time of day¨ information releasing a neuropeptide known as pigment dispersing factor (PDF), and likely changing synaptic partners by remodeling their axonal terminals in a circadian fashion. Over the years a reasonably clear picture of how the molecular clock is assembled within a cell has emerged; however, little is known about how this molecular clock communicates with other clocks in the brain and the body to ensure a coherent response to daily changes in the environment, which is the focus of our laboratory. To begin to gauge the extent of circadian control of cellular processes we sought to identify cycling genes employing a genome wide approach. Thus we revealed a role for the voltage gated, Ca2+ dependent potassium channel slowpoke in the control of rhythmic activity; interestingly, altering excitability of the circadian network differentially affected the pace of the oscillations in dorsal clusters, thereby leading to arrhythmicity (Ceriani et al. 2002; Fernández et al. 2007). During this characterization we uncovered a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions (Fernandez et al. 2008). The molecular mechanisms underlying this structural plasticity will be discussed. Electrical activity of PDF neurons is required for rhythmic rest-activity cycles, but its relevance to the maintenance of molecular oscillations is still under debate. To gain insight into this process we developed a new tool for temporal control of gene expression in PDF neurons, which was employed to silence the PDF circuit only in adults (Depetris-Chauvin et al. 2011). This novel approach allowed us to address the requirement of ion fluxes across the membrane in sustaining rhythmic behavior, and ultimately, on the molecular clock driving rest/activity cycles.