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Ephrin-As mediate targeting of eye-specific projections to the lateral geniculate nucleus

Nature Neuroscience volume 8, pages 1013–1021 (2005)Cite this article

Abstract

Axon guidance cues contributing to the development of eye-specific visual projections to the lateral geniculate nucleus (LGN) have not previously been identified. Here we show that gradients of ephrin-As and their receptors (EphAs) direct retinal ganglion cell (RGC) axons from the two eyes into their stereotyped pattern of layers in the LGN. Overexpression of EphAs in ferret RGCs using in vivo electroporation induced axons from both eyes to misproject within the LGN. The effects of EphA overexpression were competition-dependent and restricted to the early postnatal period. These findings represent the first demonstration of eye-specific pathfinding mediated by axon guidance cues and, taken with other reports, indicate that ephrin-As can mediate several mapping functions within individual target structures.

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Figure 1: Eye-specific development and ephrin-As in the ferret LGN.
Figure 2: EphAs in the postnatal ferret retina.
Figure 3: In vivo ganglion cell electroporation.
Figure 4: Effect of EphA overexpression on eye-specific targeting and comparison to activity blockade.
Figure 5: EphA overexpression causes ipsilateral eye axons to misproject into opposite eye territory.
Figure 6: Effects of EphA overexpression on targeting of individual retinogeniculate axons.
Figure 7: Ephrin-A expression in the ferret LGN is developmentally regulated.

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Acknowledgements

We thank P. Nguyen, R. Kumar, D. Van Der List and G. Woods for technical assistance, M. Greenberg for the gift of the EphA3 and EphA5 expression plasmids and Colin Akerman for permission to adapt his ferret visuotopic map diagram. This work was supported by the US National Eye Institute (NEI; EY11369 to B.C. and EY14689-01 to D.A.F.), the NEI Vision Science Training Fellowship (EY015387 to A.D.H.), NS39094 (E.G. Jones, University of California, Davis, provided support for K.D.M.) and NEI Core Grant (EY12576 to L.M. Chalupa).

Author information

Author notes

  1. Andrew D Huberman

    Present address: Department of Neurobiology, Fairchild Building, Stanford University School of Medicine, Palo Alto, California, 94305, USA

Authors and Affiliations

  1. Center for Neuroscience, 1544 Newton Ct., University of California, Davis, 95616, California, USA

    Andrew D Huberman, Karl D Murray, David K Warland & Barbara Chapman

  2. Section of Neurobiology, Physiology and Behavior, 1 Shields Ave., University of California, Davis, 95616, California, USA

    David K Warland & Barbara Chapman

  3. Department of Molecular, Cellular and Developmental Biology, 225 Sinsheimer Labs, University of California Santa Cruz, Santa Cruz, 95064, California, USA

    David A Feldheim

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Supplementary information

Supplementary Fig. 1

Model for ephrin-A induced targeting of eye-specific retinogeniculate projections. (PDF 1559 kb)

Supplementary Fig. 2

Scatter plots of the correlation index (CI) as a function of the inter-cell distance for each of the cell pairs recorded at P3. (PDF 1567 kb)

Supplementary Fig. 3

Scatter plots of the correlation index (CI) as a function of the inter-cell distance for each of the cell pairs recorded at P5. (PDF 1532 kb)

Supplementary Fig. 4

Scatter plots of the correlation index (CI) as a function of the inter-cell distance for each of the cell pairs recorded at P7. (PDF 1273 kb)

Supplementary Table 1

The Correlation Index (CI) intercept A and the correlation length L, together with their 95% confidence limits for ganglion cells recorded at each postnatal age, in control and EphA5 overexpressing ferret retinas. (PDF 54 kb)

Supplementary Movie 1

Movie of multi-site extracellular recording of spontaneous retinal activity from a control P5 ferret retina, shown at 1 frame per second; scale: X axis=1 second; Y axis=140 microVolts. Waves of activity like that shown here periodically propagate across the RGC layer of the retina. (MOV 157 kb)

Supplementary Movie 2

Movie of multi-site extracellular recording of spontaneous retinal activity from an EphA5 electroporated P5 ferret retina (electroporation was carried out on P1), shown at 1 frame per second; scale: X axis=1 second; Y axis=140 microVolts. The waves seen in EphA5 overexpressing retinas were indistinguishable from those seen in control retinas. (MOV 157 kb)

Supplementary Methods (PDF 124 kb)

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Huberman, A., Murray, K., Warland, D. et al. Ephrin-As mediate targeting of eye-specific projections to the lateral geniculate nucleus. Nat Neurosci 8, 1013–1021 (2005). https://doi.org/10.1038/nn1505

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