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Developmental regulation of glutamate receptor field size by nonvesicular glutamate release

Nature Neuroscience volume 5, pages 141–146 (2002)Cite this article

Abstract

We hypothesized that presynaptic glutamate regulates postsynaptic ionotropic glutamate receptor number during synaptogenesis. To test this idea, we genetically manipulated presynaptic glutamate levels at the glutamatergic Drosophila neuromuscular junction (NMJ), then microscopically and electrophysiologically measured postsynaptic glutamate receptor field size and function. Our data show that presynaptic glutamate is a strong negative regulator of postsynaptic receptor field size and function during development. Glutamate-triggered receptor downregulation was not affected by block of synaptic vesicle fusion, demonstrating that receptors are regulated by nonvesicular glutamate release. Our results reveal an elegant mechanism for receptor field regulation during synaptogenesis and reveal a nonpathological role for nonvesicular glutamate release at the synapse.

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Figure 1: Genetic manipulation of presynaptic glutamate levels.
Figure 2: The number of functional postsynaptic glutamate receptors are inversely proportional to pre-synaptic glutamate levels.
Figure 3: Postsynaptic glutamate receptor field area is inversely related to presynaptic glutamate level.
Figure 4: Glutamate-dependent glutamate receptor downregulation occurs via a nonvesicular release mechanism.

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Acknowledgements

Thanks to C. Schuster for glutamate receptor antibodies (8B4D2, now available from the University of Iowa Developmental Studies Hybridoma Bank, due to the donation of hybridoma cells by the lab of C. Goodman). Also thanks to the Bloomington Stock Center for Drosophila stocks, and Kei Ito for tips on making color figures visible to color-blind individuals. This work was supported by grants from the MDA and NIH (GM54544 to K.B.).

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  1. Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, 84112-0840, Utah, USA

    David E. Featherstone, Emma Rushton & Kendal Broadie

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Correspondence to David E. Featherstone or Kendal Broadie.

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Featherstone, D., Rushton, E. & Broadie, K. Developmental regulation of glutamate receptor field size by nonvesicular glutamate release. Nat Neurosci 5, 141–146 (2002). https://doi.org/10.1038/nn789

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