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Submitted on March 3, 2004
Accepted on April 19, 2004
Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release Sites
Robert T. Fremeau Jr. 1,Kaiwen Kam 2,Tayyaba Qureshi 3,Juliette Johnson 4,David R. Copenhagen 4,Jon Storm-Mathisen 3,Farrukh A. Chaudhry 3,Roger A. Nicoll 2*,Robert H. Edwards 1*
1 Departments of Neurology and Physiology, UCSF School of Medicine, CA, USA. 2 Departments of Physiology and Cellular & Molecular Pharmacology, UCSF School of Medicine, CA, USA. 3 Anatomical Institute & Centre for Molecular Biology and Neuroscience, University of Oslo, P.O. Box 1105 Blindern, N-0317 Oslo, Norway. 4 Departments of Physiology and Ophthalmology, Graduate Programs in Neuroscience and Cell Biology, UCSF School of Medicine, CA, USA.
* To whom correspondence should be addressed.
Roger A. Nicoll , E-mail: nicoll{at}cmp.ucsf.edu Robert H. Edwards , E-mail: edwards{at}itsa.ucsf.edu
Vesicular glutamate transporters (VGLUT) 1 and 2 show a mutuallyexclusive distribution in adult brain that suggests specializationfor synapses with different properties of release. Consistentwith this distribution, inactivation of the VGLUT1 gene silenceda subset of excitatory neurons in the adult. However, the samecell populations exhibited VGLUT1-independent transmission earlyin life. Developing hippocampal neurons transiently co-expressedVGLUT2 and VGLUT1 at distinct synaptic sites with differentshort-term plasticity. The loss of VGLUT1 also reduced the reservepool of synaptic vesicles. Thus, VGLUT1 plays an unanticipatedrole in membrane trafficking at the nerve terminal.
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