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SM Saszik, JG Robson, LJ Frishman; Contributions of Spiking and Non-spiking Inner Retinal Neurons to the Scotopic ERG of the Mouse . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1817.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:: The scotopic ERG near visual threshold is dominated by a negative scotopic threshold response (nSTR) and very sensitive positive waves. The present study was undertaken to determine the contributions from spiking and non-spiking ganglion and amacrine cells to these sensitive waves in the mouse ERG. Methods: ERGs were recorded from adult C57/BL6 mice anesthetized with ketamine (70 mg/kg) and xylazine (7 mg/kg). Recordings were between DTL fibers placed under contact lenses on the two eyes. Monocular test stimuli were brief flashes (λ-max 470 nm; -5.8 to 1.8 log sc td.s) under fully dark-adapted conditions. Recordings also were made following acute intravitreal injections of GABA (35 mM) to suppress all inner retinal activity, tetrodotoxin (TTX, 7.5 µM) to suppress spiking, or in animals in which ganglion cells had been lesioned either by optic nerve crush (ONC) 21 days earlier, or by NMDA (160 nMoles) injected 6 days earlier. Results: For ERG responses to brief flashes of increasing energy, amplitudes were measured at two fixed times after the flash: the peak (110 ms) of the positive potentials (b-wave), and the trough (200 ms) of slower negative (STR) potentials. These data were fit with a model assuming linear rise with stimulus strength and saturation of 5 components of increasing sensitivity: negative (n) and positive (p) STRs, a positive sensitive response (pSR), PII (bipolar cell) and PIII (photocurrent). After eliminating (with GABA) the inner retinal sensitive components: nSTR and pSTR, and pSR, the PII-bipolar cell component rose linearly, as predicted, with stimulus energy before saturating. TTX reduced nSTR sensitivity, by ∼60 times. In contrast, after ganglion cell loss (ONC, NMDA) the nSTR showed less than a 10-fold loss of sensitivity. The amplitude at 110 msec was reduced a little by TTX, and more by ganglion cell removal; the energy at which the b-wave saturated and its maximum amplitude were normal. However, both TTX and ganglion cell loss also reduced b-wave amplitude over a middle range of flash energies for which PII normally dominates the ERG. This reduction could be reversed by GABA, after which the response rose linearly with energy, suggesting that GABA suppressed an abnormal negative potential of inner retinal origin that had been induced by TTX or ganglion cell removal. Conclusion: The results show that in the dark-adapted mouse ERG the negative STR is predominately spike related, but only partly originates from ganglion cells. In contrast, ganglion cells contribute strongly to the sensitive positive scotopic responses, but these responses are only partially spike-related.
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