Impaired clock output by altered connectivity in the circadian network.

MF CERIANI

Cold Spring Harbor Laboratories, USA, Octubre 2007

Congreso; Neurobiology of Drosophila; 2007

The circadian clock serves as a temporal filter to synchronize gene expression, cell metabolism, physiology and behavior to the most critical moments in the day, thus contributing to the adaptation of the organism to a changing environment.  While substantial progress has been made in elucidating the molecular processes that impart this temporal control, much less is known about how this cellular process translates into behavioral activity at the proper time along the day. Circadian changes of the neuropeptide pigment dispersing factor (PDF) appear to be central to how the clock controls rhythmic rest-activity cycles. We have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the calcium-dependent voltage-gated potassium channel slowpoke (slo) to examine the activity of specific neuronal populations in circadian control of behavior.  We found that molecular oscillations in the pacemaker cells are properly running in the null mutant in stark contrast to what is seen in the remaining circadian relevant clusters. Lack of SLO function specifically impairs PDF accumulation on projections towards the pars intercerebralis.  Remarkably, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit.  Our observations support the notion that subtle structural changes within the circadian network could be responsible for behavioral arrhythmicity.