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Lei-Lei Liu, Nathan J Spix, Dao-Qi Zhang; NMDA receptors contribute to excitatory synaptic input to dopaminergic amacrine cells in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2974. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Dopamine plays many important roles in visual function, including light adaptation. This neuromodulator is solely released by dopaminergic amacrine cells (DACs), which receive excitatory input from rods, cones and melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). These synaptic inputs are known to be mediated by AMPA-type glutamate receptors. In the present study, we examined whether NMDA-type glutamate receptors also contribute to the DAC synaptic input.
Wild-type and transgenic/mutant mice were used for immunohistochemical staining and whole-cell voltage clamp recordings, respectively. Melanopsin-based responses of DACs were isolated by genetic deletion of rod/cone function or in retinal degeneration 1 mice in which rods and cones had degenerated.
Mg2+ is known to block NMDA receptors when the resting membrane potential is less than -40 mV. We found that removing Mg2+ from the extracellular medium significantly increased the peak amplitude of melanopsin-based responses of DACs at a holding potential of -70 mV (n=4). In the absence of Mg2+, the global NMDA receptor antagonist D-AP5 (50 μM) reduced melanopsin-based responses by 73% (n=6). We then isolated NMDA receptor-mediated melanopsin-based responses by blocking AMPA/KA receptors. We found that Con-T, a GluN2A/2B-containing receptor antagonist, almost abolished NMDA-receptor-mediated light responses (n=5), whereas the GluN2A-containing receptor antagonist NVP077 (n=3) or a GluN2B-containing receptor antagonist Con-G (n=3) partially suppressed the responses. Immunohistochemical staining suggested that both GluN2A and GluN2B subunits are expressed in DAC somas and processes. Finally, we unexpectedly observed that CNQX (100 μM), a classic AMPA/KA receptor antagonist, substantially suppressed NMDA receptor-mediated light responses of DACs (n=4).
Our results suggest that GluN2A/2B-containing NMDA receptors contribute to excitatory synaptic transmission to DACs, and may be involved in mediating synaptic plasticity of the dopaminergic network during light adaptation.
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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