@article{0407f68f846a461cbd664a04217d3021,
title = "Polyphasic circadian neural circuits drive differential activities in multiple downstream rhythmic centers",
abstract = "Circadian clocks align various behaviors such as locomotor activity, sleep/wake, feeding, and mating to times of day that are most adaptive. How rhythmic information in pacemaker circuits is translated to neuronal outputs is not well understood. Here, we used brain-wide, 24-h in vivo calcium imaging in the Drosophila brain and searched for circadian rhythmic activity among identified clusters of dopaminergic (DA) and peptidergic neurosecretory (NS) neurons. Such rhythms were widespread and imposed by the PERIOD-dependent clock activity within the ∼150-cell circadian pacemaker network. The rhythms displayed either a morning (M), evening (E), or mid-day (MD) phase. Different subgroups of circadian pacemakers imposed neural activity rhythms onto different downstream non-clock neurons. Outputs from the canonical M and E pacemakers converged to regulate DA-PPM3 and DA-PAL neurons. E pacemakers regulate the evening-active DA-PPL1 neurons. In addition to these canonical M and E oscillators, we present evidence for a third dedicated phase occurring at mid-day: the l-LNv pacemakers present the MD activity peak, and they regulate the MD-active DA-PPM1/2 neurons and three distinct NS cell types. Thus, the Drosophila circadian pacemaker network is a polyphasic rhythm generator. It presents dedicated M, E, and MD phases that are functionally transduced as neuronal outputs to organize diverse daily activity patterns in downstream circuits.",
keywords = "Drosophila, GCaMP6, calcium, circadian physiology, dopamine, neuronal pacemakers, peptidergic",
author = "Xitong Liang and Holy, {Timothy E.} and Taghert, {Paul H.}",
note = "Funding Information: We thank Holy and Taghert laboratories and the Washington University Center for Cellular Imaging (WUCCI) for advice and technical support; Mark Wu, Margaret Ho, and Tingting Xie for guidance in selecting driver lines for dopaminergic neurons; and Orie Shafer, Francois Rouyer, Larry Zipursky, Michael Rosbash, and Bloomington Stock Center provided fly stocks and reagents. The work was supported by the Washington University McDonnell Center for Cellular and Molecular Neurobiology and by NIH grants R01 NS068409 and R01 DP1 DA035081 (T.E.H.), R01 NS099332 and R01 GM127508 (P.H.T.), and R24 NS086741 (T.E.H. and P.H.T.). Funding Information: We thank Holy and Taghert laboratories and the Washington University Center for Cellular Imaging (WUCCI) for advice and technical support; Mark Wu, Margaret Ho, and Tingting Xie for guidance in selecting driver lines for dopaminergic neurons; and Orie Shafer, Francois Rouyer, Larry Zipursky, Michael Rosbash, and Bloomington Stock Center provided fly stocks and reagents. The work was supported by the Washington University McDonnell Center for Cellular and Molecular Neurobiology and by NIH grants R01 NS068409 and R01 DP1 DA035081 (T.E.H.), R01 NS099332 and R01 GM127508 (P.H.T.), and R24 NS086741 (T.E.H. and P.H.T.). X.L. T.E.H. and P.H.T. conceived the experiments; X.L. performed and analyzed all experiments; and X.L. and P.H.T. wrote the manuscript. T.E.H. has a patent on OCPI microscopy. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = jan,
day = "23",
doi = "10.1016/j.cub.2022.12.025",
language = "English",
volume = "33",
pages = "351--363.e3",
journal = "Current Biology",
issn = "0960-9822",
number = "2",
}