Department of Biology, Johns Hopkins University, Baltimore, United States
Rachel A Ross
Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States; Department of Psychiatry, Massachusetts General Hospital, Boston, United States
Preethi Somasundaram
Department of Biological Sciences, University of Marlyand, Baltimore, United States
Suja Hiriyanna
National Eye Institute, National Institutes of Health, Bethesda, United States
Zhijian Wu
National Eye Institute, National Institutes of Health, Bethesda, United States
Tudor C Badea
National Eye Institute, National Institutes of Health, Bethesda, United States
Phyllis R Robinson
Department of Biological Sciences, University of Marlyand, Baltimore, United States
Bradford B Lowell
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States; Program in Neuroscience, Harvard Medical School, Boston, United States
Department of Biology, Johns Hopkins University, Baltimore, United States; Department of Neuroscience, Johns Hopkins University, Baltimore, United States
Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters. Transient responses utilize input from rod photoreceptors and output by the classical neurotransmitter glutamate, but adapt within minutes. In contrast, sustained responses are dominated by non-conventional signaling mechanisms: melanopsin phototransduction in ipRGCs and output by the neuropeptide PACAP, which provide stable pupil maintenance across the day. These results highlight a temporal switch in the coding mechanisms of a neural circuit to support proper behavioral dynamics.