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Segmental specification of GABAergic inhibition during development of hindbrain neural networks

Nature Neuroscience volume 2, pages 873–877 (1999)Cite this article

Abstract

A primordial rhythm-generating neural network emerges during the segmental period of vertebrate hindbrain development, suggesting a common genetic basis to both the structure and network activity of the region. We show here that segmentation influenced a postsegmental developmental step by which a GABAergic rhythm generator was incorporated into the primordial network and increased rhythm frequency to near mature values. This process depended on specifications in r3 and r5 that controlled, on the basis of a two-segment repeat, later maturation of GABAergic inhibition.

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Figure 1: Initiation of high-frequency (HF) rhythm in the postsegmental hindbrain of the chick embryo correlates with development of an inhibitory–excitatory sequence in inhibited reticular neurons (IRN).
Figure 2: GABAA receptors are responsible for high-frequency rhythm.
Figure 3: Odd-rhombomeric specification of HF-CPGs.
Figure 4: Two-segment repeated specification of high-frequency activity in cranial roots.

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References

  1. Edlund, T. & Jessel, T. M. Progression from extrinsic to intrinsic signaling in cell fate specification: A view from the nervous system. Cell 96, 211–224 (1999).

    Article  CAS  Google Scholar 

  2. Lumsden, A. & Krumlauf, R. Patterning the vertebrate neuraxis. Science 274, 1109–1115 (1996).

    Article  CAS  Google Scholar 

  3. Fortin, G., Kato, F., Lumsden, A. & Champagnat, J. Rhythm generation in the segmented hindbrain of the chick embryo. J. Physiol. (Lond.) 486, 735–744 ( 1995).

    Article  CAS  Google Scholar 

  4. Champagnat, J. & Fortin, G. Primordial respiratory-like rhythm generation in the vertebrate embryo. Trends Neurosci. 20, 119–124 (1996).

    Article  Google Scholar 

  5. Hamburger, V. & Hamilton, H. L. A series of normal stages in the development of the chick embryo. J. Morphol. 88 , 49–92 (1951).

    Article  CAS  Google Scholar 

  6. Fortin, G., Foutz, A. S. & Champagnat, J. Respiratory rhythm generation in chick hindbrain: effect of MK-801 and vagotomy. Neuroreport 5, 1137 –1140 (1994).

    Article  CAS  Google Scholar 

  7. Jacquin, T. D. et al. Reorganization of pontine rhythmogenic neuronal networks in Krox-20 knockout mice. Neuron 17, 747–758 (1996).

    Article  CAS  Google Scholar 

  8. Fortin, G., Champagnat, J. & Lumsden, A. Onset and maturation of branchio-motor activities in the chick hindbrain. Neuroreport 5, 1149 –1152 (1994).

    Article  CAS  Google Scholar 

  9. Harris, N. C. & Constanti, A. Mechanism of block by ZD 7288 of the hyperpolarization-activated inward rectifying current in guinea pig substantia nigra neurons in vitro. J. Neurophysiol. 74, 2366–2378 (1995).

    Article  CAS  Google Scholar 

  10. Gasparini, S. & Di Francesco, D. Action of the hyperpolarization-activated current (I h) blocker ZD7288 in hippocampal CA1 neurons. Pflugers Arch. 435, 99– 106 (1997).

    Article  CAS  Google Scholar 

  11. Lüthi, A., Bal, T. & McCormick, D. A. Periodicity of thalamic spindle waves is abolished by ZD7288, a blocker of I h. J. Neurophysiol. 79, 3284–3289 ( 1998).

    Article  Google Scholar 

  12. Delcomyn, F. Neural basis of rhythmic behavior in animals. Science 210, 492–498 (1980).

    Article  CAS  Google Scholar 

  13. Fénelon, V. S., Casanovas, B., Simmers, J. & Meyrand, P. Development of rhythmic pattern generators. Curr. Opin. Neurobiol. 8, 705–709 ( 1998).

    Article  Google Scholar 

  14. Wilkinson, D. G., Bhatt, S., Chavrier, P., Bravo, R. & Charnay, P. Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse. Nature 337, 461–464 (1989).

    Article  CAS  Google Scholar 

  15. McGinnis, W. & Krumlauf, R. Homeobox genes and axial patterning. Cell 68, 283–302 (1992).

    Article  CAS  Google Scholar 

  16. Lumsden, A. & Keynes, R. Segmental patterns of neuronal development in the chick hindbrain. Nature 337, 424– 428 (1989).

    Article  CAS  Google Scholar 

  17. Taneja, R. et al. The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos. Dev. Biol. 177, 397–412 ( 1996).

    Article  CAS  Google Scholar 

  18. Seitanidou, T., Schneider-Manoury, S., Desmarquet, C., Wilkinson, D. G. & Charnay, P. Krox-20 is a key regulator of rhombomere-specific gene expression in the developing hindbrain. Mech. Dev. 65, 31–42 (1997).

    Article  CAS  Google Scholar 

  19. Xu, Q., Mellitzer, G., Robinson, V. & Wilkinson, D. In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399, 267– 271 (1999).

    Article  CAS  Google Scholar 

  20. Flanagan, J. G. & Vanderhaeghen, P. The ephrins and Eph receptors in neural development. Annu. Rev. Neurosci. 21, 309–345 (1998).

    Article  CAS  Google Scholar 

  21. Wan, Q. et al. Recruitment of functional GABAA receptors to postsynaptic domains by insulin. Nature 388, 686– 690 (1997).

    Article  CAS  Google Scholar 

  22. Wang, H., Bedford, F. K., Brandon, N. J., Moss, S. J. & Olsen, R. W. GABA(A)-receptor-associated protein links GABA(A) receptors and cytoskeleton. Nature 397 , 69–72 (1999).

    Article  CAS  Google Scholar 

  23. Torres, R. et al. PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron 21, 1453–1463 (1998).

    Article  CAS  Google Scholar 

  24. Xia, J., Zhang, X., Staudinger, J. & Huganir, R. L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22, 179–187 (1999).

    Article  CAS  Google Scholar 

  25. Brückner, K. et al. EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron 22, 511–524 (1999).

    Article  Google Scholar 

  26. Cherubini, E., Gaiarsa, J. L. & Ben-Ari, Y. GABA: an excitatory transmitter in early postnatal life. Trends Neurosci. 14, 515– 519 (1991).

    Article  CAS  Google Scholar 

  27. LoTurco, J. J., Owens, D. F., Heath, M. J., Davis, M. B. & Kriegstein, A. R. GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15, 1287–1298 (1995).

    Article  CAS  Google Scholar 

  28. Wagner, S., Castel, M., Gainer, H. & Yarom, Y. GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity. Nature 387, 598–603 ( 1997).

    Article  CAS  Google Scholar 

  29. Wilkinson, D. G. in In Situ Hybridisation, a Practical Approach (ed. Wilkinson, D. G.) 1–83 (IRL Press, Oxford, 1992).

    Google Scholar 

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Acknowledgements

This work was supported by CNRS, the Fondation pour la Recherche Médicale, a Human Frontier Science Program RG0101/1997-B grant to J.C. and an EEC grant to S. J. We thank V. Abadie for help with mouse-embryo recordings, V. Prince and D. Wilkinson for gifts of probes to Hoxb1 and Krox-20, respectively, and J. Gilthorpe and A. Coutinho for reading the manuscript.

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Authors and Affiliations

  1. Biologie Fonctionnelle du Neurone, Institut Alfred Fessard, C.N.R.S., 1, av. de la Terrasse, Gif-sur-Yvette, 91198, France

    Gilles Fortin & Jean Champagnat

  2. Department of Developmental Neurobiology, MRC Brain Development Programme, King's College London, Guy's Campus, London, SE1 9RT, UK

    Stefan Jungbluth & Andrew Lumsden

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  1. Gilles Fortin
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  2. Stefan Jungbluth
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  4. Jean Champagnat
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Correspondence to Gilles Fortin.

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Fortin, G., Jungbluth, S., Lumsden, A. et al. Segmental specification of GABAergic inhibition during development of hindbrain neural networks. Nat Neurosci 2, 873–877 (1999). https://doi.org/10.1038/13172

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