Orexin-A Intensifies Mouse Pupillary Light Response by Modulating Intrinsically Photosensitive Retinal Ganglion Cells

• DOI: 10.1523/jneurosci.0217-20.2021
• Publication Date: 2021-02-03T20:12:15Z
• Authors: Wei Zhou; Li-Qin Wang; Yu-Qi Shao; Xu Han; Chen-Xi Yu; Fei Yuan; Xin Wang; Shi-Jun Weng; Yong-Mei Zhong; Xiong-Li Yang
• Keywords: Male; Mice, Knockout; Retinal Ganglion Cells; Orexins; 0303 health sciences; Pyrrolidines; Pupil; Reflex, Pupillary; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Orexin Receptors; Intravitreal Injections; Animals; Benzimidazoles; Female; Photic Stimulation

We show for the first time that neuropeptide orexin modulates pupillary light response, a non-image-forming visual function, in mice of either sex. Intravitreal injection receptor (OXR) antagonist TCS1102 and orexin-A reduced enhanced constriction response to light, respectively. Orexin-A activated OX 1 Rs on M2-type intrinsically photosensitive retinal ganglion cells (M2 cells), caused membrane depolarization these by modulating inward rectifier potassium channels nonselective cation channels, thus resulting an increase intrinsic excitability. The increased excitability could account orexin-A-evoked spontaneous discharges light-induced spiking rates M2 cells, leading intensification constriction. did not alter M1 which be because no or weak expression them, as revealed RNAscope situ hybridization. In sum, is likely decrease pupil size influencing thereby improving performance awake via enhancing focal depth eye's refractive system. SIGNIFICANCE STATEMENT This study reveals role mouse function. administration intensifies increasing activating subtype R. Modulation were both involved ionic mechanisms underlying such intensification. Orexin improve reducing