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February 23, 2026 • ✎ STRIA TECH

Retinal glia regulate development of the circadian photoentrainment circuit

Disrupting SNARE function in Müller glia impairs photoentrainment

Topics:

Development

Glial Suppression

Neurodevelopment and Circuit Mechanisms

Publication

Cell Reports (Nov 25, 2025) Retinal glia regulate development of the circadian photoentrainment circuit

Brown TW, Vilallongue N, Hales SC, Srikanta S, Rochon PL, Rangel Olguin AG, Waxman SB, Tufford A, Van Prooijen J, Krishnaswamy A, Cermakian N, Cayouette M

DOI: 10.1016/j.celrep.2025 >>

The study shows that special support cells in the retina called Müller glia help guide the development of a circuit that lets light reset the body’s internal clock (circadian photoentrainment). Light information is sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs), but how these neurons form correct connections was unclear. The researchers found that during early development, Müller glia closely interact with these ipRGCs and release chemical signals like ATP that help the neurons mature properly. If this glia‑to‑neuron communication is disrupted, the light‑driven adjustment of daily rhythms is impaired, even though basic vision and pupil responses remain normal — showing that glial cells are essential for assembling the circadian light‑sensing pathway.

Circadian photoentrainment depends on intrinsically photosensitive retinal ganglion cells (ipRGCs), which convey environmental light information to the hypothalamus. While the anatomy and function of mature ipRGCs are well characterized, the mechanisms guiding their developmental integration into the circadian circuit remain unclear. Here, using transsynaptic rabies tracing in mice, we show that Müller glia are primary upstream partners of developing hypothalamus-projecting ipRGCs, suggesting a role for glia-neuron communication in the assembly of the photoentrainment pathway. We further show that disrupting SNARE function specifically in Müller glia during early postnatal development impairs ATP release, induces ipRGC hyper-responsiveness to light, and results in defective photoentrainment. In contrast, visual acuity and the pupillary light reflex, which are mediated by different RGC/ipRGC subtypes, remain unaffected. These results indicate a critical and circuit-specific role for Müller glia in shaping the development and function of the retinal pathway underlying circadian photoentrainment.