Retinal pathway origins of the pattern electroretinogram (PERG)

Abstract

Purpose. To determine retinal pathway origins of pattern electroretinogram (PERG) in macaque monkeys using pharmacologic dissections, uniform-field flashes, and PERG simulations. Methods. Transient (2 Hz, 4 reversals/s) and steady state (8.3 Hz, 16.6 reversals/s) PERGs and uniform-field ERGs were recorded before and after intravitreal injections of l-AP4 (not APB) (2-amino-4-phosphonobutyric acid, 1.6 -2.0 mM), to prevent ON pathway responses; PDA (cis-2,3-piperidinedicarboxylic acid, 3.3-3.8 mM), to block activity of hyperpolarizing second- and all third-order retinal neurons; and TTX (tetrodotoxin, 6 μM), to block Na 2-dependent spiking. PERGs were also recorded from macaques with advanced unilateral experimental glaucoma, and were simulated by averaging ON and OFF responses to uniform-field flashes. Results. For 2-Hz stimulation, l-AP4 reduced both negative- and positive-going (N 95 and P 50) amplitudes in transient PERGs, and their counterparts, N 2 and P 1 in simulations, to half-amplitude. PDA eliminated N 95 and N 2, but increased P 50 and P 1 amplitudes, in that it enhanced b-waves. As previously reported, severe experimental glaucoma or TTX eliminated photopic negative responses, N 95, and N 2; glaucoma eliminated P 50 and reduced P 1 amplitude; TTX reduced P 50 and hardly altered P 1. For 8.3-Hz stimulation, l-AP4 eliminated the steady state PERG and reduced simulated PERG amplitude, whereas PDA enhanced both responses. TTX reduced PERG amplitude to less than half; simulations were less reduced. Blockade of all postreceptoral activity eliminated transient and steady state PERGs, but left small residual P 1 in simulations. Conclusions. Transient PERG receives nearly equal amplitude contributions from ON and OFF pathways. N 95 reflects spiking activity of ganglion cells; P 50 reflects nonspiking activity as well. Steady state PERG, in contrast, reflects mainly spikerelated ON pathway activity. © 2011 The Association for Research in Vision and Ophthalmology, Inc.