Approach sensitivity in the retina processed by a multifunctional neural circuit

Abstract

The detection of approaching objects, such as looming predators, is necessary for survival. Which neurons and circuits mediate this function? We combined genetic labeling of cell types, two-photon microscopy, electrophysiology and theoretical modeling to address this question. We identify an approach-sensitive ganglion cell type in the mouse retina, resolve elements of its afferent neural circuit, and describe how these confer approach sensitivity on the ganglion cell. The circuit's essential building block is a rapid inhibitory pathway: it selectively suppresses responses to non-approaching objects. This rapid inhibitory pathway, which includes AII amacrine cells connected to bipolar cells through electrical synapses, was previously described in the context of night-time vision. In the daytime conditions of our experiments, the same pathway conveys signals in the reverse direction. The dual use of a neural pathway in different physiological conditions illustrates the efficiency with which several functions can be accommodated in a single circuit.

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Figure 1: PV-5 ganglion cells are sensitive to approaching motion.
Figure 2: PV-5 ganglion cells respond to approaching motion even in the absence of dimming.
Figure 3: Response of PV-5 ganglion cells to lateral motion is suppressed by an ON inhibitory signal.
Figure 4: PV-5 ganglion cells receive a rapid inhibitory input required to suppress responses to lateral motion.
Figure 5: PV-6 OFF ganglion cells respond to lateral motion.
Figure 6: The rapid inhibitory pathway is mediated by an electrical synapse. Unless noted, all traces on this figure are from PV-5 cells in Cx36−/− background.
Figure 7: PV-5 cells receive an inhibitory input from AII amacrine cells.
Figure 8: The functional properties of AII amacrine cells are consistent with the rapid inhibitory signal in PV-5 ganglion cells.

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Acknowledgements

We are grateful to S. Arber (Friedrich Miescher Institute), D. Paul (Harvard Medical School) and J. Sanes (Harvard University) for providing mouse lines and Robert Margolskee (Mount Sinai School of Medicine) for providing the Gγ13 antibody. We are grateful for the technical assistance of S. Djaffer, B. Gross Scherf and Y. Shimada. We thank members of the Roska lab, P. Lagali, P. Caroni, R. Friedrich and A. Lüthi for comments on the manuscript. The 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 Human Frontier Science Program Young Investigator grant, a National Centers of Competence in Research in Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., a Marie Curie Postdoctoral Fellowship to T.A.M., the Centre National de la Recherche Scientifique through the Unité Mixte de Recherche 8550 to R.A.d.S.

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T.A.M. performed electrophysiological experiments, designed experiments and model, and wrote manuscript; R.A.S. designed experiments and model and wrote manuscript; S.S. performed immunohistochemistry; T.J.V. performed electrophysiological experiments, G.B.A. performed and designed electrophysiological experiments; and B.R. designed experiments and model and wrote manuscript.

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Correspondence to Botond Roska.

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Münch, T., da Silveira, R., Siegert, S. et al. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nat Neurosci 12, 1308–1316 (2009). https://doi.org/10.1038/nn.2389

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