Intrinsically Photosensitive Retinal Ganglion Cells That Project To The Superior Colliculus Are Not Necessary For Light-Induced Changes In Breathing In Mice

Light sensed by melanopsin ( Opn4 )-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) modulates multiple, non-image forming processes including breathing. However, the specific ipRGC population(s) responsible for modulating breathing in response to environmental light has not been determined. Prior research indicates that the superior colliculus (SC) modulates respiratory rate and receives direct projections from ipRGCs of subtypes M1-M3. To determine the relative role of this ipRGC population in modulating breathing in response to light, we bilaterally co-injected a GFP-expressing marker virus and a cre-dependent, retro-AAV-expressing diphtheria toxin A into the SC of Opn4 cre/+ mice. This approach effectively ablates Opn4 -expressing ipRGCs that project to the SC target area and allows placement verification with GFP fluorescence. Tidal volume, respiratory rate, and minute ventilation were measured with whole-body plethysmography both before and after ipRGC ablation. Breathing was measured for 36 hours and spanned two 12-hr dark phases, the second of which contained a 3-hour light pulse from ZT13 to ZT16. Similar to pre-ablation, mice with verified unilateral (n = 3) and bilateral (n = 5) placement in the SC exhibited respiratory rate and minute ventilation suppression for ~90 minutes after light pulse onset, as well as an increase in tidal volume, respiratory rate, and minute ventilation for ~90 minutes after the light pulse offset. Despite the known role of the SC in modulating respiratory rate, these data suggest that M1-M3 ipRGCs projecting to the SC are not necessary for the light-induced breathing phenotype. While preliminary, these results expand our understanding of respiratory biology and suggest that a multimodal network of retinal and neuronal populations mediate respiratory changes to environmental light. This research is supported by Marquette University. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.