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Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit


Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing1,2. A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells3,4,5. It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6–8) while recording from a single genetically labelled type of DS cell9,10. We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell.

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Figure 1: Targeting of ChR2c to starburst amacrine cells at P8.
Figure 2: Monosynaptically restricted circuit mapping initiated from ON DS cells.
Figure 3: ChR2c-assisted circuit mapping at P8 and P6.
Figure 4: Development of asymmetry.


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We thank B. G. Scherf, S. Djaffer and J. Jüttner for technical assistance, T. Szikra for helping with light intensity calibration, V. Busskamp for suggesting the use of the 2A element and the cloning strategy for the 2A-based expression system, and V. Busskamp, K. Farrow, S. Oakeley and P. King for their comments on the manuscript. We thank E. Callaway for providing the rabies viruses and K. Conzelmann and S. Arber for discussion about rabies viruses. The study was supported by the Friedrich Miescher Institute for Biomedical Research, a US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant, a Marie Curie Excellence grant, a National Centre of Competence in Research Frontiers in Genetics grant, an European Research Council as well as RETICIRC, TREATRUSH and OPTONEURO grants from the European Union to B.R. and an EMBO Long-Term Fellowship to K.Y.

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K.Y. performed and designed all retinal experiments, in vivo injection experiments with rabies, herpes and AAV viruses, developed all plasmids, analysed data and wrote the paper. K. B. grew and titred rabies viruses. M.N. developed SPIG1–GFP mice. G.N. and E.B. developed ChR2c. B.R. designed experiments, analysed data and wrote the paper.

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Correspondence to Botond Roska.

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Yonehara, K., Balint, K., Noda, M. et al. Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit. Nature 469, 407–410 (2011).

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