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Steven A Barnes, Cyrus F McHugh, Shashvat Purohit, James CR Grove, Arlene A Hirano, Nicholas Brecha; Light and dopamine alter properties of horizontal cell feedback to photoreceptors in mammalian retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5264.
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© ARVO (1962-2015); The Authors (2016-present)
Horizontal cells (HCs) send feedback to photoreceptors (PRs) in mammalian retina via a mechanism involving autaptic signaling by GABA that changes synaptic cleft pH, a mechanism that couples HC depolarization or hyperpolarization with acidification-induced inhibition or alkalinization-induced disinhibition of photoreceptors, respectively. This feedback effect changes depending on how light adapted the retina is. Here we test the hypothesis that ambient light levels and dopamine regulate the properties of this feedback.
Calcium imaging and patch clamp recording were performed in rats and mice. Retinal slices loaded with fluo-4 were imaged on a confocal microscope and PR Ca2+ changes were recorded in cell bodies close to their synaptic terminals. PRs and HCs were patch clamped in retinal slices under infrared illumination. Kainate, CNQX or NBQX were used to depolarize or hyperpolarize HCs. The GABA agonist muscimol and GABA antagonists TPMPA and gabazine were used to activate or block GABARs responsible for autaptic signaling. Dopamine (DA), D1R agonist SKF-38393 and D2R antagonist spiperone were used to modulate DA pathways.
Under constant bright illumination, depolarization of HCs inhibited Ca2+ signals in PRs and hyperpolarization enhanced them, while muscimol alone enhanced them. Under low light levels, muscimol inhibited Ca2+ channel activation in PRs, but when the slices were incubated for >1 hr with DA, the polarity of this response was reversed. Since depolarization-evoked DA release might modulate ion channels in PRs directly via D2Rs and/or via D1Rs on HCs, we tested short applications of SKF-38393 and spiperone, but observed no HC-induced modulation of PR Ca2+ signals.
These results show that ambient light levels and DA regulate feedback to PRs. Modeling of this pathway suggests that signaling from HCs to PRs is in part dependent on modifiable parameters in HCs that regulate feedback properties.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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