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Rong-Shan Yan, Sheng-Nan Qiao, Yong-Mei Zhong, Dao-Qi Zhang; Cholinergic retinal waves generate slow and rhythmic depolarizations in dopaminergic amacrine cells of the developing retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4791. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The key neuromodulator dopamine is synthesized and released in the developing retina, which plays an important role in eye development. The release of retinal dopamine appears to be regulated by cholinergic retinal waves during development (Arroyo et al., 2016). Cholinergic waves are initiated by starburst amacrine cells (SACs) and propagate to neighboring SACs and retinal ganglion cells (RGCs) across the retina. However, it is unknown whether cholinergic retinal waves generate spontaneous patterned activity in dopaminergic amacrine cells (DACs), the sole source of dopamine in the retina. Here we sought to examine spontaneous activity of DACs in the developing mouse retina and to identify possible input from SACs to DACs during cholinergic waves of activity.
Whole-cell current-clamp recordings were performed from RGCs and fluorescently-labeled DACs and SACs in flat-mount retinas isolated from mice aged postnatal days 6 and 7.
DACs exhibited large spontaneous rhythmic membrane depolarizations with a rate of 0.70 ± 0.04 per min (n = 6, mean ± SE). The spontaneous depolarizations were separated by extended periods of sparse subthreshold potentials. Each depolarization had a slow onset, followed by a relatively sustained peak that was accompanied by a cluster of spikelets. The mean peak amplitude of the depolarization was 23.37 ± 2.59 mV (n = 6). Spontaneous rhythmic depolarizations were also examined in SACs and RGCs. SACs exhibited a spontaneous depolarization rate of 0.87 ± 0.07 per min (n = 3), whereas RGCs spontaneously depolarized at a rate of 0.93 ± 0.07 per min (n = 3). Nicotinic acetylcholine receptor antagonist hexamethonium, a blocker of cholinergic retinal waves, abolished the spontaneous rhythmic depolarizations in both DACs (n = 6) and RGCs (n = 3), respectively.
Our data demonstrate that spontaneous rhythmic depolarizations of DACs mirror those observed from SACs and RGCs in the first postnatal week in mice, which are likely a result of cholinergic retinal waves. The results suggest that cholinergic retinal waves appear to generate slow and rhythmic depolarizations in DACs, which drives dopamine release in the developing retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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