Class B1 Neuropeptide Modulation of Sleep/Wake Cycles

Our long‐term goal is the mechanistic dissection of neuropeptide signals in neural circuits in vivo . We have used a variety of genetic reagents for in vivo cell‐specific manipulation of three Class B1 neuropeptides whose G protein‐coupled receptors (GPCRs) signal through cAMP in fly circadian/sleep control circuits. Our studies suggest distinct important roles for these peptides in controlling daily patterns of sleep and activity. Flies adapt their bimodal crepuscular pattern of rest and activity to prevailing seasonal conditions: in the winter most activity is in the evening (to avoid the chill of night), while in the summer most activity is in the morning (to avoid the heat of day). Our preliminary studies suggest that increased autocrine activation of the GPCR for one of these peptides in the neurons that secrete this peptide themselves underlies this seasonal shift in the balance of activity from evening to morning. We present evidence that this autocrine GPCR activation induces this plastic change in circadian network properties by modulating the daily pattern of peptide secretion itself. We also present evidence that a reciprocal feedback loop between neurons secreting two different Class B1 peptides drives morning activity.