Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Abstract

The purpose of this study was to determine the contributions of postreceptoral neurons to the lightadapted ERG of the Nob mouse, a model for complete-type congenital stationary night blindness (CSNB1) that lacks a b-wave from depolarizing bipolar cells. Ganzfeld ERGs were recorded from anesthetized adult control mice, control mice injected intravitreally with L-2-amino-4-phosphonobutyric acid (Control APB mice) to remove On pathway activity, and Nob mice. ERGs also were recorded after PDA (cis-2, 3-piperidine-dicarboxylic acid, 3-5 mM) was injected to block transmission to hyperpolarizing (Off) bipolar and horizontal cells, and all 3rd order neurons. Stimuli were brief (< 4 ms, 0.4 -2.5 log sc td s) and long (200 ms, 2.5 -4.6 log sc td) LED flashes (λmax = 513 nm, on a rod suppressing background (2.6 log sc td). Sinusoidal modulation of the LEDs (mean, 2.6 log sc td; contrast, 100%; 3 to 36 Hz) was used to study flicker ERGs.Brief-flash ERGs of Nob mice presented as long-lasting negative waves with a positive-going intrusion that started about 50 ms after the flash and peaked around 120 ms. Control APB mice had similar responses, and in both cases, PDA removed the positive-going intrusion. For long flashes, PDA removed a small, slow "d-wave" after light offset. With sinusoidal stimulation, the fundamental (F1) amplitude of control mice ERG peaked at 8 Hz (~70 μV). For Nob mice the peak was ~20 μV at 6 Hz before PDA and ~10 μV at 3 Hz or lower after PDA. F1 responses were present up to 21 Hz in control and Nob eyes and 15 Hz in Nob eyes after PDA. Between 3 and 6 Hz, F1 phase was 170°-210° more delayed in Nob than control mice; phase was hardly altered by PDA. With vector analysis, a substantial postreceptoral input to the Nob flicker ERG was revealed. In control mice, the second harmonic (F2) response showed peaks of ~10 μV at 3 Hz and 13 Hz. Nob mice showed almost no F2. In summary, in this study it was found that in Nob mice, postreceptoral neurons from the Off pathway make a positive-going contribution to the light-adapted flash ERG, and contribute substantially to sinusoidal flicker ERG.

Asymmetrical Functional Deficits of ON and OFF Retinal Processing in the mdx3Cv Mouse Model of Duchenne Muscular Dystrophy

“…This allowed the contributions from both cone photoreceptors and OFF-bipolar cells to be examined. 39 Inspection of DMD waveforms (bold traces) superimposed on those of WT (thin traces) showed that the scotopic OPs, scotopic b-wave, and, minimally, the photopic b-wave may exhibit reduced amplitudes. Particularly in the scotopic signals, larger a-wave components were revealed with the reduction of the b-waves.…”

“…39 Following this component is the P ON (probably homologue to the b-wave), which reflects the ON-response. As in the measurements with the mesopic sawtooth stimuli, we confirm previous observations that stimulus offsets do not elicit a d-wave in the mouse.…”

“…33,41 Under light-adapted conditions, a photopic ERG mainly composed of a positive b-wave (at approximately 40 ms) was elicited to a moderate 2 phot cd.s/ m 2 flash. 38,39,42 Other photopic components of the short-flash ERG were not considered at this setting (see Methods). Analysis of the photopic a-wave in this section was assessed from the photopic long-flash ERG (Figs.…”

The response of the neuronal adaptive system to background illumination and readaptation to dark in the immature retina

“…Our study was neither designed to separate the ON-and OFF-components of the ERG nor the OFF-contribution to the OP response. Future studies are needed for such analysis which will require, for example, longlasting stimulus light, pharmacological dissections to identify the ON-and OFF-components of the OPs (Kojima & Zrenner 1978;Wachtmeister 1981bWachtmeister , 1998Shirato et al 2008;Raghuram et al 2013).…”

Functional and structural impact of the loss of the leucine-rich repeat protein LRIT1 in the mouse retina.

“…Thus, comparisons of a-wave measurements in wild-type and nob mice can lead to the inaccurate conclusion that the a-wave is changed. Although the awave is often measured from baseline to the trough of the wave (106), it is more directly monitored by measuring it from baseline to the amplitude at a fixed time such as 15ms after the flash if the experimental models exhibit an ablated b-wave (107). The second, positive-going corneal b-wave corresponds to ON bipolar cell depolarization, or opening of the TRPM1 cation channels allowing cation influx into the cell.…”