Purpose: The neuromodulator dopamine plays an important role in light adaptation for the visual system. Light can stimulate dopamine release from dopaminergic amacrine cells (DACs) by activating three classes of photosensitive retinal cells: rods, cones, and melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). However, the synaptic mechanisms by which these photoreceptors excite DACs remain poorly understood. Our previous work demonstrated that α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors contribute to light regulation of DAC activity. AMPA receptors are classified into Ca2+-permeable and Ca2+-impermeable subtypes. We sought to identify which subtype of AMPA receptors is involved in light regulation of DAC activity.
Methods: AMPA receptor-mediated light responses and miniature excitatory postsynaptic currents were recorded from genetically labeled DACs in mouse retinas with the whole-cell voltage-clamp mode. Immunostaining with antibodies against tyrosine hydroxylase, GluA2 (GluR2), and PSD-95 was performed in vertical retinal slices.
Results: The biophysical and pharmacological data showed that only Ca2+-impermeable AMPA receptors contribute to DAC light responses driven by ipRGCs or cones (via depolarizing bipolar cells). We further found that the same subtype of AMPA receptors mediates miniature excitatory postsynaptic currents of DACs. These findings are supported by the immunohistochemical results demonstrating that DACs express the PSD-95 with GluA2, a subunit that is essential for determining the impermeability of AMPA receptors to calcium.
Conclusions: The results indicated that GluA2-containing Ca2+-impermeable AMPA receptors contribute to signal transmission from photosensitive retinal cells to DACs.
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