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Visual map development depends on the temporal pattern of binocular activity in mice

Nature Neuroscience volume 15, pages 298–307 (2012)Cite this article

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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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Figure 1: ChR2-expressing retinal ganglion cells (RGCs) are activated with high temporal precision with blue light both in vitro and in vivo.
Figure 2: In vivo Ca2+ imaging demonstrates that most superior colliculus neurons respond to optogenetic stimuli before eye opening.
Figure 3: Synchronous but not asynchronous stimulation of both eyes disrupts eye-specific segregation in the superior colliculus.
Figure 4: Binocular stimulation asynchronous by as much as 100 ms disturbs eye segregation.
Figure 5: Synchronous stimulation disrupted eye segregation and asynchronous stimulation improved eye segregation during development in AAV-ChR2 treated mice.
Figure 6: Synchronous stimulation disrupts and asynchronous stimulation improves eye-specific segregation in ChR2;Chrnb2−/− mice.
Figure 7: Synchronous stimulation disrupts eye segregation in the dLGN.
Figure 8: Chronic stimulation of ChR2-expressing RGCs disrupts retinotopy of ipsilateral RGCs but improves retinotopy of contralateral RGCs.

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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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Authors and Affiliations

  1. Department of Neurobiology, Yale University, New Haven, Connecticut, USA,

    Jiayi Zhang, James B Ackman, Hong-Ping Xu & Michael C Crair

  2. Department of Ophthalmology & Visual Sciences, Yale University, New Haven, Connecticut, USA

    Michael C Crair

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  1. Jiayi Zhang
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Contributions

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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Correspondence to Michael C Crair.

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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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