ipRGC properties prevent light from shifting the SCN clock during daytime
Article Meta data
Article Date = 07 January 2026
Article URL = https://www.nature.com/articles/s41586-025-09894-z
Article Title = ipRGC properties prevent light from shifting the SCN clock during daytime
Article Image = https://www.nature.com/articles/s41586-025-09894-z/figures/1
Summary
This Nature paper shows that intrinsic properties of a class of retinal ganglion cells (M1 ipRGCs) limit how daylight affects the brain’s central clock, the suprachiasmatic nucleus (SCN). The authors combine chemogenetics, electrophysiology (single-cell and MEA), immunohistochemistry and behavioural wheel-running assays to demonstrate that at daytime intensities many M1 ipRGCs enter depolarisation block. That retinal “homeostatic gate” reduces the photic input to the SCN and prevents phase shifts in the circadian clock during the day. By contrast, at night the SCN gate is open and ipRGC input can shift the clock; chemogenetic activation or particular wavelengths (violet) that recruit more ipRGCs can overcome the retinal gate to produce shifts. The work establishes a two-tier gating model: a retinal, activity-dependent gate plus the established circadian (SCN) gate.
Key Points
- M1 ipRGCs show high intrinsic photosensitivity but at high, sustained daytime-like illumination many cells enter depolarisation block, suppressing sustained spiking.
- Depolarisation block acts as a retinal “homeostatic gate” that reduces the amount of photic signalling reaching the SCN during the subjective day.
- Under normal daytime conditions this retinal gate, together with the SCN’s daytime insensitivity, prevents light from phase-shifting the circadian clock.
- Chemogenetic activation of ipRGCs can overcome the retinal gate and force daytime phase shifts, demonstrating sufficiency of increased retinal input to open the SCN gate.
- Spectral composition matters: violet light drives more sustained ipRGC responses (and fewer block events) than green at high intensity, producing larger effects on SCN activation and small daytime shifts when combined with other inputs.
- Different downstream circuits are required for daytime versus nighttime phase shifts; extra-SCN projections and the lateral geniculate complex contribute to daytime signalling patterns revealed by selective manipulations.
- The authors propose an integrated model in which retinal and SCN gates together set the temporal window for photic entrainment and limit the magnitude of phase shifts.
Content summary
The study used Opn4-Cre mouse lines expressing excitatory DREADDs in ipRGCs to selectively boost retinal output and measured molecular (H3 phosphorylation, cFos), electrophysiological and behavioural endpoints. Long-duration light pulses during subjective day did not induce SCN molecular markers or phase shifts unless ipRGCs were chemogenetically activated. MEA and whole-cell recordings showed that M1 ipRGCs produce an initial burst of spikes then become suppressed at high light intensities consistent with depolarisation block; this effect was wavelength-dependent. Ablation or silencing of particular ipRGC subpopulations and of LGN circuits revealed distinct pathways required for daytime versus nighttime responses. The authors integrate these observations into a model where a retinal homeostatic gate (via ipRGC depolarisation block) complements the SCN’s circadian gating to limit photic resetting during the day and to constrain the magnitude of nocturnal shifts.
The methods are rigorous and diverse: chemogenetics, immunohistochemistry, ex vivo MEA, patch clamp, behavioural wheel-running assays, circuit manipulations and spectral stimulus controls. Data and code availability are stated; custom electrophysiology analysis code is on GitHub (SchwartzNU/SymphonyAnalysis).
Context and relevance
This paper reframes how we think about light input to the circadian system by shifting some explanatory weight from the SCN to the retina. It shows that the retina itself actively filters sustained daytime illuminations via a physiological mechanism (depolarisation block) in ipRGCs. That matters for anyone studying photic entrainment, light therapy, shift-work impacts, or the design of lighting (spectral content and intensity) aimed at influencing human circadian rhythms. The retinal gate concept may explain why daytime light often fails to shift rhythms and suggests routes to modulate retinal signalling (spectral tuning or targeted neuromodulation) to enhance or reduce entrainment effects.
Why should I read this
Short version: it’s clever and useful — the retina isn’t just a passive light sensor for the clock, it actively gates signals so daytime light usually can’t reset your central clock. If you care about circadian biology, lighting design, or why some light therapies flounder, this paper saves you time by showing the mechanism and pointing to practical ways to change it (wavelengths, boosting ipRGC output).
Author style
Punchy: the authors marshal chemogenetics, electrophysiology and behaviour to make a big conceptual shift — the retina enforces a daytime “homeostatic gate” via depolarisation block in M1 ipRGCs that works with the SCN gate to prevent light-induced resetting. For specialists this is a must-read because it changes where you look for interventions; for applied folks it flags spectral and circuit-level levers that could be exploited.