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A transient network of intrinsically bursting starburst cells underlies the generation of retinal waves

Nature Neuroscience volume 9, pages 363–371 (2006)Cite this article

Abstract

Pharmacologically isolated starburst amacrine cells (SACs) in perinatal rabbit retinas spontaneously generated semiperiodic calcium spikes and long-lasting after-hyperpolarizations (AHPs), mediated by calcium-activated, cyclic AMP–sensitive potassium currents. These AHPs, rather than a depletion of neurotransmitters (as was previously believed), produced the refractory period of spontaneous retinal waves and set the upper limit of the wave frequency. Each SAC received inputs from roughly 10–30 neighboring SACs during a wave. These inputs synchronized and reshaped the intrinsic bursts to produce network oscillations at a rhythm different from that of individual SACs. With maturation, the semiperiodic bursts in SACs disappeared, owing to reduced intrinsic excitability and increased network inhibition. Thus, retinal waves are generated by a transient and specific network of cell-autonomous oscillators synchronized by reciprocally excitatory connections.

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Figure 1: Cell-autonomous activity in E29–P1 SACs.
Figure 2: Cell-autonomous activities of SACs under Ca2+ imaging.
Figure 3: Temporal properties of the bursts in SACs.
Figure 4: The ionic mechanism of intrinsic bursts in SACs.
Figure 5: Mechanism of the postwave refractory process.
Figure 6: Network contributions to rhythmogenesis.
Figure 7: Developmental loss of intrinsic bursts in SACs.

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Acknowledgements

We thank Q. Yang and T. Mon for help with some imaging experiments and A. Hayar for discussions on cross-correlation analysis. This study was supported by US National Institutes of Health grant R01EY10894 (to Z.J.Z.), unrestricted funds from Research to Prevent Blindness Inc. and from the Pat and Willard Walker Eye Research Center, and by the University of Arkansas for Medical Sciences Tobacco Fund.

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Author notes

  1. Jijian Zheng and Seunghoon Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology and Biophysics and Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, 72205, Arkansas, USA

    Jijian Zheng, Seunghoon Lee & Z Jimmy Zhou

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Correspondence to Z Jimmy Zhou.

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Supplementary information

Supplementary Fig. 1

Cross-correlation analysis among neighboring starburst amacrine cells (SACs) under Ca2+ imaging. (PDF 96 kb)

Supplementary Fig. 2

Excitability of SACs during the slow AHP. (PDF 445 kb)

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Zheng, J., Lee, S. & Zhou, Z. A transient network of intrinsically bursting starburst cells underlies the generation of retinal waves. Nat Neurosci 9, 363–371 (2006). https://doi.org/10.1038/nn1644

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