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Nathalia Torres Jimenez, Robert F Miller, Eric Gustafson; The Synaptic Basis of the PERG. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):469.
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© ARVO (1962-2015); The Authors (2016-present)
The pattern-electroretinogram (PERG) has been used for clinical diagnosis and scientific studies of retinal function. Although it is generally agreed that the PERG is generated by ganglion cells, the contribution of ganglion cell synaptic receptors has not been resolved with clarity. Our goal is to examine the synaptic contributions of the PERG, with special emphasis on the excitatory synaptic receptors that generate ganglion cell light responses, including N-methyl-D-aspartate (NMDA) and Amino-3-hydoxy-5 methyl-4-isoxazolepropionic acid (AMPA) receptors. These two glutamatergic receptors provide the dominant, light-evoked input to retinal ganglion and amacrine cells. Since the PERG is unique in activating ganglion cells as one of its major components, we hypothesize that the PERG signal will contain a substantial NMDA and AMPA receptor contribution.
We performed extracellular recordings using an unanesthetized (after perfusion has started), perfused retina eye-cup preparation of C57/6BL male mice between 3 to 5 months of age. The group delineation is based on whether or not they received a pharmacological manipulation. Those mice in the experimental group were treated with D-AP7 (NMDAR antagonist) and NBQX (AMPAR antagonist), while also blocking inhibitory inputs using a combination of strychnine (glycine receptor antagonist), picrotoxinin (GABAR antagonist) and TPMPA (GABAcR antagonist). We generate a PERG pattern using VisionEgg software connected to a DLP projector. The image was then projected through a high powered dissecting microscope (Olympus SZX12) forming an image on the retina.
Our results indicate that the positive component of the PERG, known as the P50 in clinical literature, is largely composed of NMDA and AMPA receptor contributions.
This study highlights the importance NMDA and AMPA receptors for generation of the P component of the PERG. However, our results also demonstrate that inhibitory circuits play a major role in the PERG waveform and we continue to study how inhibitory circuitry modulates the waveform of the PERG.
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