A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction

Elife. 2016 Sep 26;5:e15392. doi: 10.7554/eLife.15392.


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.

Keywords: ipRGC; melanopsin; mouse; neuropeptides; neuroscience; neurotransmitters; retinal circuitry; vision.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Glutamic Acid / metabolism
  • Light*
  • Neurotransmitter Agents / metabolism
  • Photoreceptor Cells / physiology*
  • Photoreceptor Cells / radiation effects*
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Pupil / physiology*
  • Retinal Ganglion Cells / physiology*
  • Retinal Ganglion Cells / radiation effects*


  • Neurotransmitter Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Glutamic Acid