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Gregory William Schwartz, Jason Jacoby, Amurta Nath, Zachary Jessen; A self-regulating gap-junction network controls nitric oxide release in the retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3000.
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© ARVO (1962-2015); The Authors (2016-present)
Neuromodulators regulate circuits throughout the nervous system, and revealing the 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 plays a key role in light adaptation, but little is known about the cells that release NO.
We report the first measurements of the light responses, electrical properties, and calcium currents of the NO-releasing amacrine cell (NOAC) of the mouse retina. Our methods included electrophysiology of single cells and cell pairs, calcium imaging, immunohistochemistry, and biophysical modeling in the NEURON simulation environment.
We discover that NOACs form a dense gap- junction network, and we find that the strength of electrical coupling in the NOAC network is itself regulated by NO. A biophysical model of the NOAC network demonstrates how gap junctions control input resistance, leading to more depolarization and more NO release at high luminance.
A positive feedback loop – depolarization -> NO release -> decoupling in the NOAC network -> increased electrical resistance -> more depolarization – helps to achieve a switch-like change in NO levels at the scotopic to photopic transition. A biophysical model of the NOAC network allowed us to explore the details of this feedback loop beyond the resolution of our measurements. In addition to insights about NO release, these findings uncover a new functional role for gap junctions in regulating excitability through dynamic changes in electrical resistance.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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