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Cerebral Cortex Advance Access published online on July 2, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp133
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Vesicular Glutamate Transporter VGLUT1 Has a Role in Hippocampal Long-Term Potentiation and Spatial Reversal Learning

Detlef Balschun1, Diederik Moechars2, Zsuzsanna Callaerts-Vegh1, Ben Vermaercke1, Nathalie Van Acker3, Luc Andries3 and Rudi D'Hooge1

1 Laboratory of Biological Psychology, Department of Psychology, KU Leuven, B-3000 Leuven, Belgium, 2 Department of Functional Genomics, Johnson and Johnson Pharmaceutical Research and Development, B-2340 Beerse, Belgium, 3 Department of Pathology, Histogenex, B-2020 Antwerp, Belgium

Address correspondence to Detlef Balschun, Department of Psychology, Laboratory of Biological Psychology, Katholieke Universiteit Leuven, Tiensestraat 102, B-3000 Leuven, Belgium. Email: detlef.balschun{at}psy.kuleuven.be.

Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) show largely complementary distribution in the mature rodent brain and tend to segregate to synapses with different physiological properties. In the hippocampus, VGLUT1 is the dominate subtype in adult animals, whereas VGLUT2 is transiently expressed during early postnatal development. We generated and characterized VGLUT1 knockout mice in order to examine the functional contribution of this transporter to hippocampal synaptic plasticity and hippocampus-dependent spatial learning. Because complete deletion of VGLUT1 resulted in postnatal lethality, we used heterozygous animals for analysis. Here, we report that deletion of VGLUT1 resulted in impaired hippocampal long-term potentiation (LTP) in the CA1 region in vitro. In contrast, heterozygous VGLUT2 mice that were investigated for comparison did not show any changes in LTP. The reduced ability of VGLUT1-deficient mice to express LTP was accompanied by a specific deficit in spatial reversal learning in the water maze. Our data suggest a functional role of VGLUT1 in forms of hippocampal synaptic plasticity that are required to adapt and modify acquired spatial maps to external stimuli and changes.

Key Words: hippocampus • synaptic plasticity • VGLUT1 • VGLUT2 • water maze

Detlef Balschun, Diederik Moechars, and Zsuzsanna Callaerts-Vegh have contributed equally to this work.


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