title: Impaired clock output by altered connectivity in the circadian network.
abstract: Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.
authors: Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors: María de la Paz
authors: MP
authors: Fernández
authors: Jessie
authors: J
authors: Chu
authors: Adriana
authors: A
authors: Villella
authors: Nigel
authors: N
authors: Atkinson
authors: Steve A
authors: SA
authors: Kay
authors: María Fernanda
authors: MF
authors: Ceriani
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001683:Biological Clocks; D002940:Circadian Rhythm; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D008297:Male; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry; D009991:Oscillometry; D010641:Phenotype; D015398:Signal Transduction; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D009479:Neuropeptides