• PNAS Alerting Services
  • Sign-up for PNAS eTOC Alerts

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size

  1. S. M. Wojcik * , †,
  2. J. S. Rhee † , ‡,
  3. E. Herzog *,
  4. A. Sigler ‡,
  5. R. Jahn §,
  6. S. Takamori § , ,
  7. N. Brose * , , and
  8. C. Rosenmund ‡ , , ∥
  1. *Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Hermann-Rein Strasse 3, D-37075 Göttingen, Germany; and Departments of ‡Membrane Biophysics and §Neurobiology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany

  1. Communicated by Thomas C. Südhof, University of Texas Southwestern Medical Center, Dallas, TX, March 16, 2004 (received for review February 12, 2004)

Abstract

Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neurotransmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission.

Footnotes

  • ↵ To whom correspondence may be addressed. E-mail: rosenmun{at}bcm.tmc.edu, brose{at}em.mpg.de, or takamori{at}mpibpc.gwdg.de.

  • ↵ † S.M.W. and J.S.R. contributed equally to this work.

  • ↵ ∥ Present address: Department of Molecular and Human Genetics and Section of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030.

  • Abbreviations: VGLUT, vesicular glutamate transporter; GABA, γ-aminobutyric acid; EPSC, excitatory postsynaptic currents; mEPSC, miniature EPSC; KO, knockout.

Online Impact