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Identification of a Circadian Output Circuit for Rest:Activity Rhythms in Drosophila
Ist Teil von
Cell, 2014-04, Vol.157 (3), p.689-701
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2014
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.
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•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.