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Synapse-specific control of synaptic efficacy at the terminals of a single neuron

Abstract

The regulation of synaptic efficacy is essential for the proper functioning of neural circuits. If synaptic gain is set too high or too low, cells are either activated inappropriately or remain silent. There is extra complexity because synapses are not static, but form, retract, expand, strengthen, and weaken throughout life. Homeostatic regulatory mechanisms that control synaptic efficacy presumably exist to ensure that neurons remain functional within a meaningful physiological range1,2,3,4,5. One of the best defined systems for analysis of the mechanisms that regulate synaptic efficacy is the neuromuscular junction. It has been shown, in organisms ranging from insects to humans, that changes in synaptic efficacy are tightly coupled to changes in muscle size during development1,6,7,8. It has been proposed that a signal from muscle to motor neuron maintains this coupling9. Here we show, by genetically manipulating muscle innervation, that there are two independent mechanisms by which muscle regulates synaptic efficacy at the terminals of single motor neurons. Increased muscle innervation results in a compensatory, target-specific decrease in presynaptic transmitter release, implying a retrograde regulation of presynaptic release. Decreased muscle innervation results in a compensatory increase in quantal size.

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Figure 1: Differential expression of fasciclin II (FasII) directs synapse formation and growth.
Figure 2: Physiological consequences of increased muscle innervation.
Figure 3: The per-bouton probability of transmitter release is decreased at superinnervated muscles.
Figure 4: Quantal size is increased at muscles that receive reduced innervation.
Figure 5: Spontaneous MEJCs are independent, non-interacting events.

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References

  1. Purves, D. Body and Brain: A Trophic Theory of Neural Connections (Harvard Univ. Press, (1988)).

    Google Scholar 

  2. Miller, K. D. Synaptic economics: competition and cooperation in synaptic plasticity. Neuron 17, 371–374 (1996).

    Article  CAS  Google Scholar 

  3. Abraham, W. C. & Bear, M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19, 126–131 (1996).

    Article  CAS  Google Scholar 

  4. Bear, M. F. Asynaptic basis for memory storage in the cerebral cortex. Proc. Natl Acad. Sci. USA 93, 13453–13459 (1996).

    Article  ADS  CAS  Google Scholar 

  5. Marder, E., Abbott, L. F., Turrigiano, G. G., Zheng, L. & Golowasch, J. Memory from the dynamics of intrinsic membrane currents. Proc. Natl Acad. Sci. USA 93, 13481–13486 (1996).

    Article  ADS  CAS  Google Scholar 

  6. Magrassi, L., Purves, D. & Lichtman, J. W. Visualization of neuromuscular junctions over periods of several months in living mice. J. Neurosci. 7, 1215–1222 (1987).

    Article  Google Scholar 

  7. Govind, C. K. & Pierce, J. Remodelling of multiterminal innervation by nerve terminal sprouting in an identifiable lobster motoneuron. Science 212, 1522–1524 (1981).

    Article  ADS  CAS  Google Scholar 

  8. Schuster, C. M., Davis, G. W., Fetter, R. F. & Goodman, C. S. Genetic dissection of structural and functional components of synaptic plasticity: Fasciclin II controls synaptic stabilization and growth. Neuron 17, 641–654 (1996).

    Article  CAS  Google Scholar 

  9. Frank, E. Matching of facilitation at the neuromuscular junction of the lobster: a possible case for influence of muscle on nerve. J. Physiol. 233, 635–658 (1973).

    Article  CAS  Google Scholar 

  10. Keshishian, H. et al. Cellular mechanisms governing synaptic development in Drosophila melanogaster. J. Neurobiol. 24, 575–787 (1995).

    Google Scholar 

  11. Grenningloh, G., Rehm, E. J. & Goodman, C. S. Genetic analysis of growth cone guidance in Drosophila: Fasciclin II functions as a neuronal recognition molecule. Cell 67, 45–57 (1991).

    Article  CAS  Google Scholar 

  12. Lin, D. M. & Goodman, C. S. Ectopic and increased expression of Fasciclin II alters motoneuron growth cone guidance. Neuron 13, 507–523 (1994).

    Article  CAS  Google Scholar 

  13. Davis, G. W., Schuster, C. M. & Goodman, C. S. Genetic analysis of the molecular mechanisms controlling target selection: target derived Fasciclin II regulates the pattern of synapse formation. Neuron 19, 561–573 (1997).

    Article  CAS  Google Scholar 

  14. O'Kane, C. & Gehring, W. J. Detection in situ of genomic regulatory elements in drosophila. Proc. Natl Acad. Sci. USA 84, 9123–9127 (1987).

    Article  ADS  CAS  Google Scholar 

  15. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  Google Scholar 

  16. Jan, L. Y. & Jan, Y. Y. Properties of the larval neuromuscular junction in Drosophila melanogaster. J. Physiol. (Lond.) 262, 189–214 (1976).

    Article  CAS  Google Scholar 

  17. Stewart, B. A., Schuster, C. M., Goodman, C. S. & Atwood, H. L. Homeostasis of synaptic transmission in Drosophila with genetically altered nerve terminal morphology. J. Neurosci. 16, 3877–3886 (1996).

    Article  CAS  Google Scholar 

  18. Schuster, C. M., Davis, G. W. & Goodman, C. S. Genetic dissection of structural and functional components of synaptic plasticity: Fasciclin II controls structural plasticity. Neuron 17, 655–667 (1996).

    Article  CAS  Google Scholar 

  19. Stewart, B. A., Atwood, H. L., Renger, J. J., Wang, J. & Wu, C. F. Improved stability of Drosophila larval neuromuscular preparations in haemolymph-like physiological solutions. J. Comp. Physiol. 175, 175–191 (1994).

    Article  Google Scholar 

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Acknowledgements

We thank R. S. Zucker for technical advice and encouragement; C. Schuster for advice during early stages of this project; D. Lin for Gal-4 lines; and K. Zito and A. DiAntonio for reading the manuscript. G.W.D. is a postdoctoral associate and C.S.G. is an Investigator with the HHMI. This work was supported by an NIH grant (to C.S.G.).

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Correspondence to Graeme W. Davis.

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Davis, G., Goodman, C. Synapse-specific control of synaptic efficacy at the terminals of a single neuron. Nature 392, 82–86 (1998). https://doi.org/10.1038/32176

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