Abstract
Binocular competition is thought to drive eye-specific segregation in the developing visual system, potentially through Hebbian synaptic learning rules that are sensitive to correlations in afferent activity. Altering retinal activity can disrupt eye-specific segregation, but little is known about the temporal features of binocular activity that modulate visual map development. We used optogenetic techniques to directly manipulate retinal activity in vivo and identified a critical period before eye opening in mice when specific binocular features of retinal activity drive visual map development. Synchronous activation of both eyes disrupted segregation, whereas asynchronous stimulation enhanced segregation. The optogenetic stimulus applied was spatially homogenous; accordingly, retinotopy of ipsilateral projections was markedly perturbed, but contralateral retinotopy was unaffected or even improved. These results provide direct evidence that the synchrony and precise temporal pattern of binocular retinal activity during a critical period in development regulates eye-specific segregation and retinotopy in the developing visual system.
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Acknowledgements
We would like to thank members of the Crair laboratory for comments on the manuscript, J. Cardin and M. Higley for experimental guidance and Y. Zhang for technical help. This work was supported by US National Institutes of Health grants P30 EY000785, R01 EY015788 and R01 EY015788S to M.C.C. and by a Research to Prevent Blindness Challenge Grant to the Department of Ophthalmology & Visual Sciences. J.Z. was supported by a Brown-Coxe Fellowship. M.C.C. also thanks the family of W. Ziegler III for their support.
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J.Z. and M.C.C. designed the experiments. J.Z. conducted the stimulation experiments and analyzed the anatomical data. J.A. and J.Z. conducted the calcium imaging experiments and analyzed the data. H.-P.X. and J.Z. conducted the multielectrode array experiments and analyzed the data. J.Z. and M.C.C. wrote the manuscript.
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Zhang, J., Ackman, J., Xu, HP. et al. Visual map development depends on the temporal pattern of binocular activity in mice. Nat Neurosci 15, 298–307 (2012). https://doi.org/10.1038/nn.3007
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DOI: https://doi.org/10.1038/nn.3007
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