PURPOSE. The rat is currently being recognized as a useful animal model for studying neuroprotective strategies against retinal ganglion cell (RGC) death. The scotopic threshold response (STR) of the dark-adapted electroretinogram (ERG) of rats could be potentially useful for monitoring the electrophysiological activity of RGCs in vivo. The purpose of this study was to determine whether the STR of the rat reflects the activity of inner-retinal neurons as previously shown in cats and monkeys. METHOD. Dark-adapted ERGs were recorded differentially between DTL fiber electrodes from anesthetized Harlan Sprague-Dawley rats before and after intravitreal injection of tetrodotoxin (TTX, 4 micro liters of 40 micro molar concentration) to block sodium-dependent spikes of inner-retinal neurons. The stimuli consisted of brief (<4ms) full field blue LED flashes (peak output at 470nm, 40nm width at half-height) of intensities ranging between -5 and 2 log scot cd.s/sq m.
RESULTS. In the control responses, at lower intensities, the ERG consisted of a slow negative potential (STR) that had maximal amplitude around 250 ms at a flash intensity of -4.1 log scot cd.s/sq m. With increase in flash intensity, a positive potential could be seen emerging from the leading edge of the STR. Typical scotopic a- and b-waves were seen at higher flash intensities. Following intravitreal injection of TTX, the slow negative potential at the lower intensities (up to -4.1 log scot cd.s/sq m) was completely eliminated. At slightly higher intensities (up to -3.98 log scot cd.s/sq m) where the control responses were predominantly of the form of slow negative potentials, the post TTX responses consisted of an early negative potential followed by a positive potential with maximum amplitudes around 110 and 300ms respectively. At even higher intensities, the peak amplitude of the b-wave was slightly increased relative to control responses and the early negative response disappeared as the b-wave grew in size. No significant changes were observed with the a-wave.
CONCLUSIONS. The STR of the rat contains contributions from the spiking activity of inner-retinal neurons as previously shown in cats and monkeys.