A Self-Regulating Gap Junction Network of Amacrine Cells Controls Nitric Oxide Release in the Retina

Neuron. 2018 Dec 5;100(5):1149-1162.e5. doi: 10.1016/j.neuron.2018.09.047. Epub 2018 Oct 25.


Neuromodulators regulate circuits throughout the nervous system, and revealing the cell types and stimulus conditions controlling their release is vital to understanding their function. The effects of the neuromodulator nitric oxide (NO) have been studied in many circuits, including in the vertebrate retina, where it regulates synaptic release, gap junction coupling, and blood vessel dilation, but little is known about the cells that release NO. We show that a single type of amacrine cell (AC) controls NO release in the inner retina, and we report its light responses, electrical properties, and calcium dynamics. We discover that this AC forms a dense gap junction network and that the strength of electrical coupling in the network is regulated by light through NO. A model of the network offers insights into the biophysical specializations leading to auto-regulation of NO release within the network.

Keywords: Connexin-45; NOS; amacrine cell; gap junctions; light adaptation; nNOS; nNOS-2; nitric oxide; retina.

Publication types

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

MeSH terms

  • Amacrine Cells / cytology
  • Amacrine Cells / metabolism*
  • Animals
  • Calcium / metabolism
  • Female
  • Gap Junctions / metabolism*
  • Male
  • Mice, Transgenic
  • Models, Neurological
  • Neurites / metabolism
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type I / metabolism
  • Photic Stimulation
  • Retina / cytology
  • Retina / metabolism*


  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Calcium