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Published October 20, 2023 | Published
Journal Article Open

Immediate responses to ambient light in vivo reveal distinct subpopulations of suprachiasmatic VIP neurons

  • 1. ROR icon California Institute of Technology


The circadian rhythm pacemaker, the suprachiasmatic nucleus (SCN), mediates light entrainment via vasoactive intestinal peptide (VIP) neurons (SCN^(VIP)). Yet, how these neurons uniquely respond and connect to intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin (Opn4) has not been determined functionally in freely behaving animals. To address this, we first used monosynaptic tracing from SCN^(VIP) neurons in mice and identified two SCN^(VIP) subpopulations. Second, we recorded calcium changes in response to ambient light, at both bulk and single-cell levels, and found two unique activity patterns in response to high- and low-intensity blue light. The activity patterns of both subpopulations could be manipulated by application of an Opn4 antagonist. These results suggest that the two SCN^(VIP) subpopulations connect to two types of Opn4-expressing ipRGCs, likely M1 and M2, but only one is responsive to red light. These findings have important implications for our basic understanding of non–image-forming circadian light processing.

Copyright and License

© 2023 The Authors. Under a Creative Commons license Attribution-NonCommercial-NoDerivs 4.0 International


We thank the Gradinaru Lab for helpful discussions; Dr. Yu Li Ni, Dr. Zeynep Turan, and Martin Tran for their technical assistance with retinal extraction and processing; Dr. Corinne Beier and Prof. Erik Herzog for the helpful discussions; and Prof. Andrew Steele, Prof. Daniel Wagenaar, Ariane Helou and Catherine Oikonomou for the helpful discussions and manuscript review. Figures created with BioRender.com. 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. is supported by a Caltech Division of Biology and Biological Engineering postdoctoral fellowship. P.K. is supported by the Swiss National Science Foundation, grants P2EZP3_181896 and P500PB_203063.


Conceptualization, A.K. and V.G.; Methodology, A.K., Software, A.K., A.W., and P.K.; Investigation, A.K., K.M., and S.D.; Writing – Original Draft, A.K.; Writing – Review and Editing, A.K., K.M., S.D., and V.G.; Visualization A.K.; Funding Acquisition, V.G.; Supervision, A.K. and V.G.

Conflict of Interest

We support inclusive, diverse, and equitable conduct of research.

The authors declare no competing interests.

Data Availability

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
  • All original code has been deposited at GitHub and is publicly available as of the date of publication. DOIs are listed in the key resources table.
  • Microscopy, FP and single-cell data reported in this paper will be shared by the lead contact upon request.


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Additional details

September 29, 2023
January 9, 2024