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Cellular/Molecular

Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1

Nathan R. Wilson, Jiansheng Kang, Emily V. Hueske, Tony Leung, Helene Varoqui, Jonathan G. Murnick, Jeffrey D. Erickson and Guosong Liu
Journal of Neuroscience 29 June 2005, 25 (26) 6221-6234; DOI: https://doi.org/10.1523/JNEUROSCI.3003-04.2005
Nathan R. Wilson
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Jiansheng Kang
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Emily V. Hueske
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Tony Leung
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Helene Varoqui
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Jonathan G. Murnick
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Jeffrey D. Erickson
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Guosong Liu
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  • - July 27, 2005

Abstract

A fundamental question in synaptic physiology is whether the unitary strength of a synapse can be regulated by presynaptic characteristics and, if so, what those characteristics might be. Here, we characterize a newly proposed mechanism for altering the strength of glutamatergic synapses based on the recently identified vesicular glutamate transporter VGLUT1. We provide direct evidence that filling in isolated synaptic vesicles is subject to a dynamic equilibrium that is determined by both the concentration of available glutamate and the number of vesicular transporters participating in loading. We observe that changing the number of vesicular transporters expressed at hippocampal excitatory synapses results in enhanced evoked and miniature responses and verify biophysically that these changes correspond to an increase in the amount of glutamate released per vesicle into the synaptic cleft. In addition, we find that this modulation of synaptic strength by vesicular transporter expression is endogenously regulated, both across development to coincide with a maturational increase in vesicle cycling and quantal amplitude and by excitatory and inhibitory receptor activation in mature neurons to provide an activity-dependent scaling of quantal size via a presynaptic mechanism. Together, these findings underscore that vesicular transporter expression is used endogenously to directly regulate the extent of glutamate release, providing a concise presynaptic mechanism for controlling the quantal efficacy of excitatory transmission during synaptic refinement and plasticity.

  • VGLUT1
  • glutamate release
  • quantal size
  • homeostatic
  • excitatory
  • vesicular transporter
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The Journal of Neuroscience: 25 (26)
Journal of Neuroscience
Vol. 25, Issue 26
29 Jun 2005
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Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1
Nathan R. Wilson, Jiansheng Kang, Emily V. Hueske, Tony Leung, Helene Varoqui, Jonathan G. Murnick, Jeffrey D. Erickson, Guosong Liu
Journal of Neuroscience 29 June 2005, 25 (26) 6221-6234; DOI: 10.1523/JNEUROSCI.3003-04.2005

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Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1
Nathan R. Wilson, Jiansheng Kang, Emily V. Hueske, Tony Leung, Helene Varoqui, Jonathan G. Murnick, Jeffrey D. Erickson, Guosong Liu
Journal of Neuroscience 29 June 2005, 25 (26) 6221-6234; DOI: 10.1523/JNEUROSCI.3003-04.2005
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