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The Journal of Neuroscience, August 20, 2003, 23(20):7621-7629

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Developmental Modulation of Retinal Wave Dynamics: Shedding Light on the GABA Saga

Evelyne Sernagor,¹ Carol Young,¹ and Stephen J. Eglen²

¹School of Neurology, Neurobiology, and Psychiatry, Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, United Kingdom, and ²Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110

Embryonic spontaneous activity, in the form of propagating waves, is crucial for refining visual connections. To study what aspects of this correlated activity are instructive, we must first understand how their dynamics change with development and what factors trigger their disappearance after birth. Here we report that in the turtle retina, GABA, rather than glutamate and acetylcholine, influences developmental changes in wave dynamics. Using calcium imaging of the ganglion cell layer, we report how waves switch from fast and broad, when they emerge, to slow and narrow a few days before hatching, coinciding with the emergence of excitatory GABA_A receptor-mediated activity. Around hatching, waves gradually become stationary patches, whereas GABA_A shifts from excitatory to inhibitory, coinciding with the upregulation of the cotransporter KCC2, suggesting that changes in intracellular chloride underlie the shift. Dark-rearing from hatching causes correlated spontaneous activity to persist, whereas GABA_A responses remain excitatory, and KCC2 expression is weaker. We conclude that GABA plays an important regulatory role during the maturation of retinal neural activity. Using a simple and elegant mechanism, namely the switch from excitatory to inhibitory, GABA_A receptor-mediated activity is necessary and sufficient to cause retinal waves to stop propagating, ultimately leading to the disappearance of correlated spontaneous activity. Moreover, our results suggest that visual experience modulates the GABAergic switch.

Key words: retinal waves; retinal development; GABA; calcium imaging; dark-rearing; visual experience; spontaneous activity

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Received Dec. 27, 2002; revised Jun. 24, 2003; accepted Jul. 2, 2003.

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