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.

Highlights

  • Retinal synaptic connections and function are developmentally regulated

  • ERGs responding to 8 different light intensities were recorded from D12/2 and wild type (WT) mice at the age of postnatal day 30 (P30) and the amplitudes of the three major components, a-wave, b-wave and oscillatory potentials (OPs), were plotted as a function of stimulating light intensity to form the intensity-response curves

  • The P30/P13 ratios of ERG awave amplitudes of WT and D12/2 mice have a similar distribution pattern at most light intensities and the distribution curves are not systematically different except a few sporadic points of light intensities where either WT or D12/2 mice have higher ratio. These results demonstrated that the a-wave amplitudes increase from P13 to P30 for both WT and D12/2 mice and mutation of dopamine D1 receptor has limited effect on the maturation of photoreceptor light response

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Summary

Introduction

Retinal synaptic connections and function are developmentally regulated These developmental regulations are reflected in changes of density of synapses, expression of neurotransmitter receptors, re-organization of synaptic inputs of different synaptic pathways, excitability and light responsiveness of retinal neurons during development. Dark rearing increases the density of conventional synapses in the inner plexiform layer (IPL) of mouse and rat retinas [19,20] and delayed the bipolar cell morphological maturation in rabbits [21]. Dark rearing retarded the maturation of the strength of spontaneous RGC synaptic inputs, the age-dependent segregation of ON and OFF inputs to RGCs, light-evoked responsiveness of RGCs [17,18,23,24,25] and the age-dependent expression of GABA and glutamate receptors of retinal neurons [26,27,28,29]. Despite the evidence that visual deprivation alters maturational changes in retinal synaptic structures and functions, little is known about the synaptic and molecular mechanisms of activity-dependent developmental regulation of retinal light evoked responses

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