GABAergic and glycinergic systems regulate ON–OFF electroretinogram by cooperatively modulating cone pathways in the amphibian retina

Abstract

The network mechanisms underlying how inhibitory circuits regulate ON‐ and OFF‐responses (the b‐ and d‐waves) in the electroretinogram (ERG) remain unclear. The purpose of this study was to investigate the contribution of inhibitory circuits to the emergence of the b‐ and d‐waves in the full‐field ERG in the newt retina. To this end, we investigated the effects of several synaptic transmission blockers on the amplitudes of the b‐ and d‐waves in the ERG obtained from newt eyecup preparations. Our results demonstrated that (a) L‐APB blocked the b‐wave, indicating that the b‐wave arises from the activity of ON‐bipolar cells (BCs) expressing type six metabotropic glutamate receptors; (b) the combined administration of UBP310/GYKI 53655 blocked the d‐wave, indicating that the d‐wave arises from the activity of OFF‐BCs expressing kainate‐/AMPA‐receptors; (c) SR 95531 augmented both the b‐ and the d‐wave, indicating that GABAergic lateral inhibitory circuits inhibit both ON‐ and OFF‐BC pathways; (d) the administration of strychnine in the presence of SR 95531 attenuated the d‐wave, and this attenuation was prevented by blocking ON‐pathways with L‐APB, which indicated that the glycinergic inhibition of OFF‐BC pathway is downstream of the GABAergic inhibition of the ON‐system; and (e) the glycinergic inhibition from the ON‐ to the OFF‐system widens the response range of OFF‐BC pathways, specifically in the absence of GABAergic lateral inhibition. Based on these results, we proposed a circuitry mechanism for the regulation of the d‐wave and offered a tentative explanation of the circuitry mechanisms underlying ERG formation.

Electrophysiologic and Morphologic Strain Differences in a Low-Dose NaIO3-Induced Retinal Pigment Epithelium Damage Model

“…46 , 48 Many other potential initiating targets exist, including third-order neuronal cells, 48 cone cells, 17 ON-bipolar cells, and amacrine cell responses. 49 NaIO 3 may change the resistance of the RPE cells or other layers, directly affecting current flow and voltage differences measured in the ERG. 50 These possibilities are now testable under our conditions.…”

Synaptotagmin-9 In Mouse Retina

“…These results led us to consider the possibility that loss of Syt9 might also interfere with GABA and/or glycine release from retinal neurons. Like effects of global deletion of Syt9, blocking GABA A receptors with bicuculline typically enhances ERG b-waves (Arnarsson and Eysteinsson, 1997; Gottlob et al, 1988; Hirasawa et al, 2021; Vitanova et al, 2001). By contrast, loss of GABA C receptors and application of GABA C antagonists have been found to reduce ERG b-waves (Kapousta-Bruneau, 2000; Moller and Eysteinsson, 2003; Wang et al, 2015).…”

“…This suggests that if Syt9 is modulating GABA release, it is likely to be acting predominantly at synapses possessing GABA A receptors. Blocking glycine receptors with strychnine can also increase ERG b-waves (Arnarsson and Eysteinsson, 1997; Popova, 2000), although this has not been seen in every preparation (Hirasawa et al, 2021).…”