Dopamine D1 Receptors Regulate the Light Dependent Development of Retinal Synaptic Responses

Abstract

Retinal synaptic connections and function are developmentally regulated. Retinal synaptic activity plays critical roles in the development of retinal synaptic circuitry. Dopamine receptors have been thought to play important roles in the activity-dependent synaptic plasticity in central nervous system. The primary goal of this study is to determine whether dopamine D1 receptor regulates the activity-dependent development of retinal light responsiveness. Accordingly, we recorded electroretinogram from wild type mice and mice with genetic deletion of D1 dopamine receptor (D1−/− mice) raised under cyclic light conditions and constant darkness. Our results demonstrated that D1−/− mice have reduced amplitudes of all three major components of electroretinogram in adulthood. When the relative strength of the responses is considered, the D1−/− mice have selective reduction of the amplitudes of a-wave and oscillatory potentials evoked by low-intermediate intensities of lights. During postnatal development, D1−/− mice have increased amplitude of b-wave at the time of eye-opening but reduced developmental increase of the amplitude of b-wave after eye opening. Light deprivation from birth significantly reduced the amplitudes of b-wave and oscillatory potentials, increased the outer retinal light response gain and altered the light response kinetics of both a- and b-waves of wild type mice. In D1−/− mice, the effect of dark rearing on the amplitude of oscillatory potentials was diminished and dark rearing induced effects on the response gain of outer retina and the kinetics of a-wave were reversed. These results demonstrated roles of dopamine D1 receptor in the activity-dependent functional development of mouse retina.

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina

“…These values compare closely to waveform amplitudes seen in mice at around P10 (mouse age equivalence to human newborns), with our recorded a-wave averages 19.86 ± 2.28 μV by P10. Additionally, these values compare closely to similar in-vivo studies in mice showing a-wave amplitudes around 50 μV in P13 mice, right at the time of eye opening (19). Taken together, these data suggest that light-mediated effects on the development of the mouse visual system could be a correlate of a light-mediated effect on the development of the human visual system.…”

“…Physiological studies in the outer retina of young adult mice using electroretinograms (ERGs) and suction electrode techniques have been performed over the past few decades (10-18). Findings have confirmed that photoresponses mature over the few weeks following eye-opening (P12-P14), becoming relatively stable in terms of kinetics and sensitivity around P30 (adults) (14, 19). Relatively few experiments have been done in the developing mouse retina prior to eye opening.…”

“…Smaller a-wave deflections in young mice (P8-P10) were expected, considering the low expression profiles of a number of critical players in the phototransduction cascade [(33) and for a review, see Swaroop, Kim (40)]. Two ERG studies in the anesthetized P13 mouse pup found an approximately 50μV a-wave response to a bright white light stimulus, which would have activated, both m-opsin cones and rods (17, 19). …”

Dopamine D1 Receptors Contribute Critically to the Apomorphine-Induced Inhibition of Form-Deprivation Myopia in Mice

“…45 We also found that suppression of the b-wave and summed OP amplitudes by the D1R antagonist SCH39166 resembled the ERG phenotype of the D1R-KO mice. Similar results showing a reduction of the b-wave amplitude have been obtained by other authors working with D1R-KO mice 44,46,47 and D1R antagonist-treated goldfish. 41 However, in frogs, pharmacologic blockage of D1Rs increased the amplitudes of b-waves of both dark-and light-adapted ERGs.…”

Dynamic response to initial stage blindness in visual system development

“…All these lines of evidence suggest that the retina may act as an intact connection to the anterior segment optic system as well as the visual cortex during early visual development (sketch map shown in Figure 7a). The 'bridge' role of the retina may be functionally consistent with that of dopamine receptors, which are thought to regulate synapse formation, synaptic transmission and light adaptation in the experience-dependent development of the retina [44,45].…”