title: Pigment dispersing factor-dependent and -independent circadian locomotor behavioral rhythms.
abstract: Circadian pacemaker circuits consist of ensembles of neurons, each expressing molecular oscillations, but how circuit-wide coordination of multiple oscillators regulates rhythmic physiological and behavioral outputs remains an open question. To investigate the relationship between the pattern of oscillator phase throughout the circadian pacemaker circuit and locomotor activity rhythms in Drosophila, we perturbed the electrical activity and pigment dispersing factor (PDF) levels of the lateral ventral neurons (LNv) and assayed their combinatorial effect on molecular oscillations in different parts of the circuit and on locomotor activity behavior. Altered electrical activity of PDF-expressing LNv causes initial behavioral arrhythmicity followed by gradual long-term emergence of two concurrent short- and long-period circadian behavioral activity bouts in approximately 60% of flies. Initial desynchrony of circuit-wide molecular oscillations is followed by the emergence of a novel pattern of period (PER) synchrony whereby two subgroups of dorsal neurons (DN1 and DN2) exhibit PER oscillation peaks coinciding with two activity bouts, whereas other neuronal subgroups exhibit a single PER peak coinciding with one of the two activity bouts. The emergence of this novel pattern of circuit-wide oscillator synchrony is not accompanied by concurrent change in the electrical activity of the LNv. In PDF-null flies, altered electrical activity of LNv drives a short-period circadian activity bout only, indicating that PDF-independent factors underlie the short-period circadian activity component and that the long-period circadian component is PDF-dependent. Thus, polyrhythmic behavioral patterns in electrically manipulated flies are regulated by circuit-wide coordination of molecular oscillations and electrical activity of LNv via PDF-dependent and -independent factors.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, California 92612, USA.
authors.forename: Vasu
authors.initials: V
authors.lastname: Sheeba
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Gu
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.forename: Diane K
authors.initials: DK
authors.lastname: O'Dowd
authors.forename: Todd C
authors.initials: TC
authors.lastname: Holmes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009043:Motor Activity / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D015843:Serpins / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D001710:Biotin; D029721:Drosophila Proteins; D005136:Eye Proteins; D049452:Green Fluorescent Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D015222:Sodium Channels; D000099174:Pigment Epithelium-Derived Factor; C070614:neurobiotin