Abstract
Neurotransmitters are essential for interneuronal signalling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signalling proteins. Here we show that altering the distinct patterns of Ca2+ spike activity spontaneously generated by different classes of embryonic spinal neurons in vivo changes the transmitter that neurons express without affecting the expression of markers of cell identity. Regulation seems to be homeostatic: suppression of activity leads to an increased number of neurons expressing excitatory transmitters and a decreased number of neurons expressing inhibitory transmitters; the reverse occurs when activity is enhanced. The imposition of specific spike frequencies in vitro does not affect labels of cell identity but again specifies the expression of transmitters that are inappropriate for the markers they express, during an early critical period. The results identify a new role of patterned activity in development of the central nervous system.
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Acknowledgements
We thank D. Berg, D. Feldman, M. Feller and A. Ghosh for comments on the manuscript, T. Jessell for discussions, and I-T. Hsieh for technical support. This work was supported by a grant to N.C.S. from the National Institutes of Health. S.B.S. was supported by the NSF and Merck.
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Supplementary information
Supplementary Figure 1
Coactively spiking clusters of MNs in the embryonic neural tube.
Supplementary Figure 2
The cellular organization of the neural tube appears normal following bilateral suppression of Ca2+ spike activity.
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Borodinsky, L., Root, C., Cronin, J. et al. Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429, 523–530 (2004). https://doi.org/10.1038/nature02518
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DOI: https://doi.org/10.1038/nature02518
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