A critical role of the strychnine-sensitive glycinergic system in spontaneous retinal waves of the developing rabbit

In the developing vertebrate retina, spontaneous electric activity occurs rhythmically in the form of propagating waves and is believed to play a critical role in activity-dependent visual system development, including the establishment of precise retinal and geniculate circuitry. To elucidate how spontaneous retinal waves encode specific developmental cues at various developmental stages, it is necessary to understand how the waves are generated and regulated. Using Ca2+ imaging and patch clamp in a flat-mount perinatal rabbit retinal preparation, this study demonstrates that, in addition to the cholinergic system, a strychnine-sensitive system in the inner retina plays an obligatory and developmentally regulated role in the initiation and propagation of spontaneous retinal waves. This system, which is believed to be the glycinergic network, provided an excitatory drive during early retinal development. It then became inhibitory after postnatal day 1 (P1) to P2, an age when a number of coordinated transitions in neurotransmitter systems occurred concomitantly, and finally contributed to the complete inhibition and disappearance of spontaneous waves after P7-P9. This glycinergic contribution was notably distinct from that of the ionotropic GABAergic system, which was found to exert an inhibitory but nonessential influence on the early wave formation. Blocking glycine- and GABA-gated anion currents had opposing effects on spontaneous retinal waves between embryonic day 29 and P0, suggesting that Cl- transporters, particularly R(+)-butylindazone-sensitive K-Cl cotransporters, may have a synapse- and/or cell type-specific distribution pattern, in addition to an age-dependent expression pattern in the inner retina. Overall, the results revealed an important reliance of spontaneous retinal waves on dynamic and coordinated interactions among multiple, nonredundant neurotransmitter systems.