Cellular and Circuit Dynamics Underlying Circadian Timekeeping
Song, Bryan Joohyun
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CitationSong, Bryan Joohyun. 2020. Cellular and Circuit Dynamics Underlying Circadian Timekeeping. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractCircadian clocks internally represent the passage of each day, and organize physiology and behavior to align with changing external conditions. The central organizers of circadian rhythms are molecular oscillators that enable individual cells to track time autonomously. Clock neuron networks also represent the passage of time, with distinct ensembles active at different times of day. While the general organization of molecular oscillators has been solved, it remains unclear how clock neurons populations transition reliably and accurately between network activity states.
To address this gap in knowledge, we used Drosophila melanogaster to search for cellular and circuit mechanisms that account for differences between daytime and nighttime behavioral states. Flies undergo an internal switch in how light is contextualized: a light pulse during the night evokes a startle-like response (increased locomotor activity), but the same stimulus during the day causes locomotor quiescence. Genetic perturbance of molecular oscillators revealed that circadian clocks differentially modify behavioral responsiveness to light during daytime vs. nighttime. Optogenetic silencing experiments further showed distinct roles for two clock neuron subpopulations: LNvs contextualize light during the day, while DN1as do so during the night. Anatomical and functional investigation revealed that LNvs and DN1as form a mutually inhibitory microcircuit. Structural plasticity occurs at the presynaptic terminals of both populations, which is poised to redistribute activity between LNv and DN1a subpopulations. Rho1 pathway manipulations that interfere with remodeling also prevent transitions between light-responsive states. Together these results support a model where structural plasticity shifts the balance of activity between specialized subpopulations.
In summary, this work provides new evidence that a representation of ~24 hours is functionally distributed across clock neuron subpopulations. Further our results imply that internal time representations might be updated by daily changes to neurite morphology. The cellular and circuit motifs we identify may be generally useful to explain how behavioral states can pendulate over long timescales.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365792
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