June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Spiking dopaminergic amacrine cells strongly modulate ON-cone bipolar cell surrounds and direct signaling from horizontal cells to ON-cone bipolar cells.
Author Affiliations & Notes
  • Stuart C Mangel
    Dept of Neuroscience, Ohio State Univ Coll of Med, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Stuart Mangel, None
  • Footnotes
    Support  Plum Foundation Grant
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2225. doi:
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      Stuart C Mangel; Spiking dopaminergic amacrine cells strongly modulate ON-cone bipolar cell surrounds and direct signaling from horizontal cells to ON-cone bipolar cells.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2225.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Surround light responses are strongest following bright illumination. ON-cone bipolar cells (ON-cBCs) produce surround responses that are 1) mediated by their dendritic GABAARs and 2) modulated by the ambient light level, via activation of their dendritic dopamine D1Rs, which regulate GABAAR expression and activity (Chaffiol et al., submitted). TTX (blocks sodium spiking) greatly reduces ganglion cell surround responses (Cook, McReynolds, 1998; Taylor, 1999), suggesting that spiking neurons, which are only in the inner retina, play a significant role in surround responses. Because dopaminergic amacrine cells (DACs) in the inner retina, the only retinal neurons that release dopamine (Witkovsky, 2004), spike in response to light stimulation (Zhang et al., 2007), we studied whether spiking DACs, acting via D1Rs, modulate the strength of ON-cBC surrounds.

Methods : ON-cBC surround light responses and the effects of artificially polarizing horizontal cells (HCs) on simultaneously-recorded nearby ON-cBCs in rabbit retinal slices were studied in the day in the presence and absence of gabazine (GBZ, GABAAR antagonist), SCH23390 (SCH, D1R antagonist), APB (blocks cone input to ON-cBCs), and TTX (HCs: sharp pipettes; ON-cBCs: gramicidin perforated patch pipettes).

Results : Following maintained (30 min) bright illumination, double labeling of rabbit retinal sections with bd-17 (labels GABAARs-β2/3 subunit) and Goa (labels ON-BCs) revealed that ON-cBC dendritic GABAAR expression was significantly greater under control conditions and in the presence of both TTX and dopamine, compared to TTX alone. ON-cBCs exhibited surround light responses and polarization of HCs had a sign-conserving effect on nearby ON-cBCs when the superfusate contained dopamine, TTX, and APB, but not when the superfusate also contained GBZ or SCH. These data show that TTX acts upstream of dopamine and GBZ.

Conclusions : These findings indicate that light-evoked release of dopamine from spiking DACs, by activating D1Rs on ON-cBC dendrites, strongly modulates ON-cBC surround strength. GABAAR-mediated ON-cBC surround responses and direct sign-conserving GABAAR-mediated signaling from HCs to ON-cBCs are strongest following maintained bright illumination when spiking-evoked dopamine release and D1R activation are high, but minimal when spiking is blocked with TTX or when D1Rs are blocked.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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