Dysregulated mammalian estrus cycle rescued by timed activation of VIP neurons in the circadian pacemaker and late afternoon light exposure
Abstract
Jet lag and shift work disrupt the menstrual cycle and decrease fertility. The circadian pacemaker, the suprachiasmatic nucleus (SCN), is known to modulate ovulation, but the mechanism is unclear. Here we explore this connection by tracking the dynamics of vasoactive intestinal peptide (VIP)-expressing neurons in the SCN in freely-behaving mice. We show that SCNVIPactivity is time-of-day- and sex-dependent, and estrous-state-dependent in late afternoon, gating downstream activation of GnRH neurons. Afternoon light, as well as specific activation of SCNVIPneurons, rescues estrous cycle regularity and egg release in animals in altered light conditions, emphasizing the role of SCNVIPneurons as a time-dependent light-responsive switch. Our results reveal the dynamic mechanism by which SCNVIPneurons mediate light responses to regulate estrous states and demonstrate light-induced fertility rescue.One Sentence SummaryModulating and recording the activity of suprachiasmatic VIP neurons in freely behaving mice reveals their regulation of fertility by mediating the response to late afternoon light.
Additional Information
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. We would like to thank the Gradinaru lab for helpful discussions; Nikhila Swarna, Shinae Park, and Nathan Appling, for their technical assistance; Prof. Greg Anderson for the GnRH-Ab; Prof. Lance Kriegsfeld for the helpful discussions; and Dr. Catherine Oikonomou for the helpful discussions and manuscript review. This work was funded by the Heritage Medical Research Institute, the Vallee Foundation, and the Center for Molecular and Cellular Neuroscience in the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech (to V.G.). A.K. was supported by a Caltech Biology and Biological Engineering divisional postdoctoral fellowship and the Hebrew University Postdoctoral Fellowship for Women, Israel. A.K. acknowledges the support of her husband and children. A.K. and M.B were partially supported by the Global Grand Challenges grant from Bill & Melinda Gates Foundation. G.M.C. was supported by a PGS458 D scholarship from the National Science and Engineering Research Council (NSERC) of Canada. B.W.B. acknowledges support from the Moore Distinguished Scholar Program at Caltech. Author contributions A.K., G.M.C., M.B., and V.G. conceived the study. A.K., G.M.C., and M.B. performed the experiments, B.W.B. and A.K. developed the ML mathematical approach. A.K. analyzed and visualized the data. A.K. wrote the first draft of the manuscript. All authors read, reviewed, edited, and approved the final version of the manuscript. Data Availability and Code Availability. All data that support the findings of this study are available from the corresponding author on reasonable request. All codes for the data analysis are available at GradinaruLab/SCN‐VIP‐estrous‐cycle: Anat Kahan, Jan 2023 (github.com) The authors have declared no competing interest.Attached Files
Submitted - 2023.01.14.524075v1.full.pdf
Supplemental Material - media-1.pdf
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Additional details
- Alternative title
- Estrus cycle rescued by afternoon activation of suprachiasmatic VIP neurons
- Eprint ID
- 120151
- Resolver ID
- CaltechAUTHORS:20230316-182503000.37
- Heritage Medical Research Institute
- Vallee Foundation
- Tianqiao and Chrissy Chen Institute for Neuroscience
- Caltech Division of Biology and Biological Engineering
- Hebrew University Postdoctoral Fellowship for Women
- Bill and Melinda Gates Foundation
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Gordon and Betty Moore Foundation
- Created
-
2023-03-18Created from EPrint's datestamp field
- Updated
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2023-03-18Created from EPrint's last_modified field
- Caltech groups
- Heritage Medical Research Institute, Tianqiao and Chrissy Chen Institute for Neuroscience, Division of Biology and Biological Engineering