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J Physiol Volume 586, Number 16, 3783-3793, August 15, 2008 DOI: 10.1113/jphysiol.2008.155879
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Tonic activation of GLUK5 kainate receptors decreases neuroblast migration in whole-mounts of the subventricular zone

Jean-Claude Platel1, Tristan Heintz1, Stephanie Young1, Valerie Gordon1 and Angélique Bordey1

1 Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University, New Haven, CT 06520-8082, USA

In the postnatal subventricular zone (SVZ), neuroblasts migrate in chains along the lateral ventricle towards the olfactory bulb. AMPA/kainate receptors as well as metabotropic glutamate receptors subtype 5 (mGluR5) are expressed in SVZ cells. However, the cells expressing these receptors and the function of these receptors remain unexplored. We thus examined whether SVZ neuroblasts express mGluR5 and Ca2+-permeable kainate receptors in mouse slices. Doublecortin (DCX)-immunopositive cells (i.e. neuroblasts) immunostained positive for mGluR5 and GLUK5-7-containing kainate receptors. RT-PCR from ~10 GFP-fluorescent cell aspirates obtained in acute slices from transgenic mice expressing green fluorescent protein (GFP) under the DCX promoter showed mGluR5 and GLUK5 receptor mRNA in SVZ neuroblasts. Patch-clamp data suggest that ~60% of neuroblasts express functional GLUK5-containing receptors. Activation of mGluR5 and GLUK5-containing receptors induced Ca2+ increases in 50% and 60% of SVZ neuroblasts, respectively, while most neuroblasts displayed GABAA-mediated Ca2+ responses. To examine the effects of these receptors on the speed of neuroblast migration, we developed a whole-mount preparation of the entire lateral ventricle from postnatal day (P) 20–25 DCX-GFP mice. The GABAA receptor (GABAAR) antagonist bicuculline increased the speed of neuroblast migration by 27%, as previously reported in acute slices. While the mGluR5 antagonist MPEP did not affect the speed of neuroblast migration, the homomeric and heteromeric GLUK5 receptor antagonists, NS3763 and UB302, respectively, increased the migration speed by 38%. These data show that although both GLUK5 receptor and mGluR5 activations increase Ca2+ in neuroblasts, only GLUK5 receptors tonically reduce the speed of neuroblast migration along the lateral ventricle.

(Received 25 April 2008; accepted after revision 18 June 2008; first published online 19 June 2008)
Corresponding author A. Bordey: Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, FMB 422, New Haven, CT 06520-8082, USA.  Email: angelique.bordey{at}yale.edu


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