Identification of a Circadian Output Circuit for Rest:Activity Rhythms in Drosophila

• Published in: Cell Vol. 157; no. 3; pp. 689 - 701
• Main Authors: Cavanaugh, Daniel J., Geratowski, Jill D., Wooltorton, Julian R.A., Spaethling, Jennifer M., Hector, Clare E., Zheng, Xiangzhong, Johnson, Erik C., Eberwine, James H., Sehgal, Amita
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.04.2014
• Subjects: Animals; Animals, Genetically Modified; Brain - cytology; Brain - physiology; Circadian Clocks; Circadian Rhythm; Drosophila - cytology; Drosophila - physiology; Neurons - cytology; Neurons - physiology; Single-Cell Analysis; Transcriptome
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2014.02.024

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. [Display omitted] •Activation or ablation of subsets of PI neurons degrades rest:activity rhythms•Molecular oscillations in clock cells are unaffected by PI cell manipulations•GRASP analysis delineates a circuit connecting pacemaker neurons to PI output cells•The CRF homolog, DH44, is a circadian output molecule expressed by PI cells The Drosophila pars intercerebralis couples the circadian clock to daily rhythms of rest and activity through the release of the corticotropin-releasing factor homolog, DH44.