ORCID

http://orcid.org/0000-0002-7537-1004

Date of Award

Winter 12-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Animals show circadian rhythms in a variety of physiological functions and behaviors. In Drosophila melanogaster, behavioral rhythms are driven by circadian clock genes that are oscillating in ~150 circadian pacemaker neurons. To explain how circadian neurons encode time and regulate different behavioral rhythms, I performed 24-hour in vivo whole-brain calcium imaging using light-sheet microscopy. First, I found that different groups of circadian neurons show circadian rhythms in spontaneous neural activity with diverse phases. The neural activity phases of the M and E pacemaker groups, which are associated with the morning and evening locomotor activities respectively, occur ~4 hours before their respective behaviors. I also showed that neural activity rhythms are generated by circadian clock gene oscillations, which regulate the expression of IP3R and T-type calcium channels. Next, I asked how the diverse phases of neural activity are generated from the in-phase clock gene oscillations. Groups of circadian neurons inhibit each other via long-duration neuromodulation, mediated by neuropeptides PDF and sNPF, such that their activity phases are properly staggered across the day and night. Certain activity phases are also regulated by environmental light inputs. I then identified an output pathway by which circadian neurons regulate the locomotor activity rhythm. M and E pacemaker groups independently activate a common pre-motor center (termed ellipsoid body ring neurons) through the agency of specific dopaminergic interneurons. Finally, using methods including whole-brain pan-neuronal imaging, I further identified several output circuits downstream of circadian neurons. Circadian neural activity rhythms propagate through these circuits to regulate different behavioral outputs including sleep, olfaction, mating, and feeding rhythms. Together, my findings show how circadian clocks regulate diverse behavioral outputs by two steps; first, circadian clock genes generate diverse circadian neural activity rhythms within a network of interacting pacemaker neurons; then, sequentially-active pacemaker neurons independently and together regulate diverse behavioral outputs by generating diverse circadian neural activity rhythms in different downstream output circuits.

Language

English (en)

Chair and Committee

Paul Timothy H. Taghert Holy

Committee Members

Martha Bagnall, Erik Herzog, Daniel Kerschensteiner,

Comments

Permanent URL: https://doi.org/10.7936/zccv-3y38

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