Identification of a circadian output circuit for rest:activity rhythms in Drosophila.
Though much is known about the cellular and molecular components of the circadian clock, output pathways that couple clock cells to overt behaviors have not been identified. We conducted a screen for circadian-relevant neurons in the Drosophila brain and report here that cells of the pars intercerebralis (PI), a functional homolog of the mammalian hypothalamus, comprise an important component of the circadian output pathway for rest:activity rhythms. GFP reconstitution across synaptic partners (GRASP) analysis demonstrates that PI cells are connected to the clock through a polysynaptic circuit extending from pacemaker cells to PI neurons. Molecular profiling of relevant PI cells identified the corticotropin-releasing factor (CRF) homolog, DH44, as a circadian output molecule that is specifically expressed by PI neurons and is required for normal rest:activity rhythms. Notably, selective activation or ablation of just six DH44+ PI cells causes arrhythmicity. These findings delineate a circuit through which clock cells can modulate locomotor rhythms.
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
Daniel J
DJ
Cavanaugh
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jill D
JD
Geratowski
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
Julian R A
JR
Wooltorton
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jennifer M
JM
Spaethling
Department of Biology, Wake Forest University, Winston-Salem, NC 27109, USA.
Clare E
CE
Hector
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
Xiangzhong
X
Zheng
Department of Biology, Wake Forest University, Winston-Salem, NC 27109, USA.
Erik C
EC
Johnson
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
James H
JH
Eberwine
Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA; Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: amita@mail.med.upenn.edu.
Amita
A
Sehgal
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology / Q000502:physiology; D057906:Circadian Clocks; D002940:Circadian Rhythm; D004330:Drosophila / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D059010:Single-Cell Analysis; D059467:Transcriptome