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Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit

Abstract

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.

References

  1. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J. Physiol. (Lond.) 160, 106–154 (1962)

    CAS  Article  Google Scholar 

  2. Barlow, H. B. & Hill, R. M. Selective sensitivity to direction of movement in ganglion cells of the rabbit retina. Science 139, 412–414 (1963)

    ADS  CAS  Article  Google Scholar 

  3. Fried, S. I., Munch, T. A. & Werblin, F. S. Mechanisms and circuitry underlying directional selectivity in the retina. Nature 420, 411–414 (2002)

    ADS  CAS  Article  Google Scholar 

  4. Euler, T., Detwiler, P. B. & Denk, W. Directionally selective calcium signals in dendrites of starburst amacrine cells. Nature 418, 845–852 (2002)

    ADS  CAS  Article  Google Scholar 

  5. Lee, S. & Zhou, Z. J. The synaptic mechanism of direction selectivity in distal processes of starburst amacrine cells. Neuron 51, 787–799 (2006)

    CAS  Article  Google Scholar 

  6. Bamann, C., Gueta, R., Kleinlogel, S., Nagel, G. & Bamberg, E. Structural guidance of the photocycle of channelrhodopsin-2 by an interhelical hydrogen bond. Biochemistry 49, 267–278 (2010)

    CAS  Article  Google Scholar 

  7. Berndt, A., Yizhar, O., Gunaydin, L. A., Hegemann, P. & Deisseroth, K. Bi-stable neural state switches. Nature Neurosci. 12, 229–234 (2008)

    Article  Google Scholar 

  8. Radu, I. et al. Conformational changes of channelrhodopsin-2. J. Am. Chem. Soc. 131, 7313–7319 (2009)

    CAS  Article  Google Scholar 

  9. Yonehara, K. et al. Identification of retinal ganglion cells and their projections involved in central transmission of information about upward and downward image motion. PLoS ONE 4, e4320 (2009)

    ADS  Article  Google Scholar 

  10. Yonehara, K. et al. Expression of SPIG1 reveals development of a retinal ganglion cell subtype projecting to the medial terminal nucleus in the mouse. PLoS ONE 3, e1533 (2008)

    ADS  Article  Google Scholar 

  11. Vaney, D. I. & Taylor, W. R. Direction selectivity in the retina. Curr. Opin. Neurobiol. 12, 405–410 (2002)

    CAS  Article  Google Scholar 

  12. Barlow, H. B. & Levick, W. R. The mechanism of directionally selective units in rabbit’s retina. J. Physiol. (Lond.) 178, 477–504 (1965)

    CAS  Article  Google Scholar 

  13. Demb, J. B. Cellular mechanisms for direction selectivity in the retina. Neuron 55, 179–186 (2007)

    CAS  Article  Google Scholar 

  14. Fried, S. I., Munch, T. A. & Werblin, F. S. Directional selectivity is formed at multiple levels by laterally offset inhibition in the rabbit retina. Neuron 46, 117–127 (2005)

    CAS  Article  Google Scholar 

  15. Ariel, M. & Daw, N. W. Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells. J. Physiol. (Lond.) 324, 161–185 (1982)

    CAS  Article  Google Scholar 

  16. Masland, R. H. & Ames, A., III Responses to acetylcholine of ganglion cells in an isolated mammalian retina. J. Neurophysiol. 39, 1220–1235 (1976)

    CAS  Article  Google Scholar 

  17. Chan, Y. C. & Chiao, C. C. Effect of visual experience on the maturation of ON-OFF direction selective ganglion cells in the rabbit retina. Vision Res. 48, 2466–2475 (2008)

    Article  Google Scholar 

  18. Chen, M., Weng, S., Deng, Q., Xu, Z. & He, S. Physiological properties of direction-selective ganglion cells in early postnatal and adult mouse retina. J. Physiol. (Lond.) 587, 819–828 (2009)

    CAS  Article  Google Scholar 

  19. Elstrott, J. et al. Direction selectivity in the retina is established independent of visual experience and cholinergic retinal waves. Neuron 58, 499–506 (2008)

    CAS  Article  Google Scholar 

  20. Tian, N. & Copenhagen, D. R. Visual deprivation alters development of synaptic function in inner retina after eye opening. Neuron 32, 439–449 (2001)

    CAS  Article  Google Scholar 

  21. Hattar, S., Liao, H. W., Takao, M., Berson, D. M. & Yau, K. W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295, 1065–1070 (2002)

    ADS  CAS  Article  Google Scholar 

  22. Oyster, C. W., Takahashi, E. & Collewijn, H. Direction-selective retinal ganglion cells and control of optokinetic nystagmus in the rabbit. Vision Res. 12, 183–193 (1972)

    CAS  Article  Google Scholar 

  23. Simpson, J. I. The accessory optic system. Annu. Rev. Neurosci. 7, 13–41 (1984)

    CAS  Article  Google Scholar 

  24. Sun, W., Deng, Q., Levick, W. R. & He, S. ON direction-selective ganglion cells in the mouse retina. J. Physiol. (Lond.) 576, 197–202 (2006)

    CAS  Article  Google Scholar 

  25. Ivanova, E., Hwang, G. S. & Pan, Z. H. Characterization of transgenic mouse lines expressing Cre recombinase in the retina. Neuroscience 165, 233–243 (2010)

    CAS  Article  Google Scholar 

  26. Tang, W. et al. Faithful expression of multiple proteins via 2A-peptide self-processing: a versatile and reliable method for manipulating brain circuits. J. Neurosci. 29, 8621–8629 (2009)

    CAS  Article  Google Scholar 

  27. Wickersham, I. R. et al. Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons. Neuron 53, 639–647 (2007)

    CAS  Article  Google Scholar 

  28. Stepien, A. E., Tripodi, M. & Arber, S. Monosynaptic rabies virus reveals premotor network organization and synaptic specificity of cholinergic partition cells. Neuron 68, 456–472 (2010)

    CAS  Article  Google Scholar 

  29. Roska, B. & Werblin, F. Vertical interactions across ten parallel, stacked representations in the mammalian retina. Nature 410, 583–587 (2001)

    ADS  CAS  Article  Google Scholar 

  30. Münch, T. A. et al. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nature Neurosci. 12, 1308–1316 (2009)

    Article  Google Scholar 

  31. Atasoy, D., Aponte, Y., Su, H. H. & Sternson, S. M. A. FLEX switch targets channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping. J. Neurosci. 28, 7025–7030 (2008)

    CAS  Article  Google Scholar 

  32. Trichas, G., Begbie, J. & Srinivas, S. Use of the viral 2A peptide for bicistronic expression in transgenic mice. BMC Biol. 6, 40 (2008)

    Article  Google Scholar 

  33. Sena-Esteves, M., Tebbets, J. C., Steffens, S., Crombleholme, T. & Flake, A. W. Optimized large-scale production of high titer lentivirus vector pseudotypes. J. Virol. Methods 122, 131–139 (2004)

    CAS  Article  Google Scholar 

  34. Marshel, J. H., Mori, T., Nielsen, K. J. & Callaway, E. M. Targeting single neuronal networks for gene expression and cell labeling in vivo. Neuron 67, 562–574 (2010)

    CAS  Article  Google Scholar 

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Acknowledgements

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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The authors declare no competing financial interests.

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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). https://doi.org/10.1038/nature09711

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