Pharmacologically Induced Wave-Like Activity in the Adult Retina

Abstract

Purpose: : Spontaneous bursting activity in the developing retina propagates as waves, driving the refinement and segregation of visual pathways. This activity diminishes upon maturation and it remains unclear if its underlying mechanisms are lost thereafter. In our study we show that such waves can be pharmacologically reinitiated in the adult retina.

Methods: : Extracellular recordings were obtained with an 8x8 multi-electrode array from ex vivo isolated retina preparation while intracellular recording were achieved by the patch-clamp technique. Drugs were bath-applied through an active perfusion system. Single-cell bursting periods were detected and bursting spatiotemporal patterns analyzed.

Results: : When the first compound was bath applied, 48% of adult retinal ganglion cells (RGCs) generated periodical burst-like discharges which resembled periodic bursting activity in immature retina. Unlike short intermittent bursts typically observed in mature RGCs, they had longer burst duration (1.3±0.2 vs. 0.05±0.023 s) and inter-burst interval (31.8±28.4 s). Such bursting activity was recorded from morphologically identified RGCs and amacrine cells. Subsequent application of strychnine strongly potentiated the patterned activity by increasing burst frequency and amplitude. The proportion of bursting RGCs increased to 62%. Strychnine-induced enhancement of burst discharges was accompanied by grouping of single bursts into series of 3-10 bursting discharges separated by longer intergroup intervals, similar to those observed at late postnatal retinal development.

Conclusions: : Retinal waves can be reinitiated pharmacologically in the adult retina with similar spatial and temporal properties characteristic for the immature retina. Our results show that in the adult retina the wave-generating circuits are confined to the inner retinal layer. We suggest that the mechanisms underlying spontaneous patterned activity during development can be reinitiated in the adult retina.

Keywords: retina