July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Dopamine decreases excitatory inputs to ON sustained ganglion cells via both D1 and D4 receptor-dependent pathways
Author Affiliations & Notes
  • Michael Flood
    Physiological Sciences, University of Arizona, Tucson, Arizona, United States
  • Erika D Eggers
    Physiology, University of Arizona, Tucson, Arizona, United States
    Biomedical Engineering, University of Arizona, Tucson, Arizona, United States
  • Footnotes
    Commercial Relationships   Michael Flood, None; Erika Eggers, None
  • Footnotes
    Support  NIH Grant EY026027-03
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 557. doi:
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      Michael Flood, Erika D Eggers; Dopamine decreases excitatory inputs to ON sustained ganglion cells via both D1 and D4 receptor-dependent pathways. Invest. Ophthalmol. Vis. Sci. 2019;60(9):557.

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

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Abstract

Purpose : Previous research has demonstrated diverse modulatory effects of dopamine on ganglion cell excitability, but has not characterized the relative contribution of dopamine D1 and D4 receptors to light adaptation. The purpose of this study was to 1) determine the differential effects of D1 and D4 signaling pathways on excitatory inputs to ganglion cells, and 2) identify whether the site of action for each is presynaptic or postsynaptic to ganglion cells.

Methods : Retinas were isolated from 5-6 week old C57BL/6J male mice and cut into 250 µm thick slices. Whole-cell voltage clamp recordings of light-evoked (L) and spontaneous (s) excitatory post synaptic currents (EPSCs) were made from ON sustained ganglion cells. Light responses were elicited at multiple intensities by a 30ms full-field LED stimulus (λ = 525 nm). D1 and D4 receptors were agonized with the agonists SKF-38393 (20 µM) and PD-168077 maleate (500 nM) respectively. All experiments were performed under infrared illumination to preserve retinal sensitivity. The peak amplitude and charge transfer (Q) were measured for all evoked responses and analyzed by 2-way ANOVA. Amplitude and frequency were calculated for all sEPSCs and analyzed via paired t-test.

Results : Treatment with a D4R agonist (n=3) caused significant declines in both response peak (p<0.001) and Q (p<0.001), while the D1R agonist (n=5) caused significant declines in peak (p=0.044) but not Q (p=0.727). We found that D1 agonist treatment did not decrease response amplitudes or Qs to the same extent as light adaptation (p<0.001). D4 agonist treatment did decrease response peaks to near light adapted levels (p=0.964), but not Q (p<0.001). For sEPSCs, we did not find evidence for D1 agonist induced changes in frequency (p=0.125) or amplitude (p=0.459). We also did not find significant changes in sEPSCs induced by our D4 agonist, although they did tend towards significance (frequency p=0.076; amplitude p=0.068). This suggests that dopamine-induced adaptation is not attributable to changes at the ganglion cell level.

Conclusions : Both D1 and D4 receptors appear to play complimentary roles in modulating light adaptation at the ganglion cell level. These changes appear to be presynaptic to ganglion cells, potentially at the level of photoreceptors and inhibitory circuitry of the inner plexiform layer.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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