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Genetic address book for retinal cell types

Abstract

The mammalian brain is assembled from thousands of neuronal cell types that are organized in distinct circuits to perform behaviorally relevant computations. Transgenic mouse lines with selectively marked cell types would facilitate our ability to dissect functional components of complex circuits. We carried out a screen for cell type–specific green fluorescent protein expression in the retina using BAC transgenic mice from the GENSAT project. Among others, we identified mouse lines in which the inhibitory cell types of the night vision and directional selective circuit were selectively labeled. We quantified the stratification patterns to predict potential synaptic connectivity between marked cells of different lines and found that some of the lines enabled targeted recordings and imaging of cell types from developing or mature retinal circuits. Our results suggest the potential use of a stratification-based screening approach for characterizing neuronal circuitry in other layered brain structures, such as the neocortex.

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Figure 1: Retinal cell types and their stratification properties.
Figure 2: Cell type–specific GFP expression in the outer retina.
Figure 3: IPL stratum–specific GFP expression of amacrine cell types (some also have ganglion types labeled).
Figure 4: Identification of GENSAT mice with GFP-labeled amacrine cell types.
Figure 5: Identification of GFP-labeled ganglion cell types.
Figure 6: Stratification analysis of different cell types.

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Acknowledgements

We thank M. Ciminelli, P. Dyer, S. Djaffer, J. Hall and Y. Shimada for technical assistance, and F. Rijli, P. S. Lagali and K. Farrow for comments on the manuscript. This study was supported by Friedrich Miescher Institute funds, a US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant, a Marie Curie Excellence grant, a National Center for Competence in Research in Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., and by National Institute of Neurological Disorders and Stroke contracts N01NS02331 and HHSN271200723701C to N.H. N.H. is an Howard Hughes Medical Institute investigator.

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Authors

Contributions

Mice were produced at Rockefeller University by N.H. and K.D.P., and eyes were analyzed at the Friedrich Miescher Institute by S.S, B.G.S and B.R. The web-based retina database was developed by N.D.

Corresponding author

Correspondence to Botond Roska.

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Supplementary Figures 1–8, Supplementary Tables 1–10 and Supplementary Introduction (PDF 3778 kb)

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Siegert, S., Scherf, B., Del Punta, K. et al. Genetic address book for retinal cell types. Nat Neurosci 12, 1197–1204 (2009). https://doi.org/10.1038/nn.2370

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