Tonic activation of GLU_K5 kainate receptors decreases neuroblast migration in whole‐mounts of the subventricular zone

Abstract

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 Ca 2+ -permeable kainate receptors in mouse slices. Doublecortin (DCX)-immunopositive cells (i.e. neuroblasts) immunostained positive for mGluR5 and GLU K5−7 -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 GLU K5 receptor mRNA in SVZ neuroblasts. Patch-clamp data suggest that ∼60% of neuroblasts express functional GLU K5 -containing receptors. Activation of mGluR5 and GLU K5 -containing receptors induced Ca 2+ increases in 50% and 60% of SVZ neuroblasts, respectively, while most neuroblasts displayed GABA A -mediated Ca 2+ 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 GABA A receptor (GABA A R) 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 GLU K5 receptor antagonists, NS3763 and UB302, respectively, increased the migration speed by 38%. These data show that although both GLU K5 receptor and mGluR5 activations increase Ca 2+ in neuroblasts, only GLU K5 receptors tonically reduce the speed of neuroblast migration along the lateral ventricle.

From progenitors to integrated neurons: Role of neurotransmitters in adult olfactory neurogenesis

“…2 we did not find any difference in neuroblast migration rate either with DNQX/APV nor NPS2390 antagonists. These results are in agreement with previous studies showing that NMDA and metabotropic glutamate receptors are not involved in RMS neuroblast migration (Platel et al, 2008b;Platel et al, 2010). However while Platel et al (2008) show increase speed rate following inhibition of Glu K5 -containing kainate receptors we did not find any regulation on neuroblast migration by DNQX/APV antagonists.…”

“…Functional expression of AMPA or NMDA receptors has not been detected in astrocyte-like cells (Liu et al, 2005;, while their expression on C-type cells still needs to be investigated. Neuroblasts have been shown to express functional mGluR5 and Glu K5 -containing kainate receptors, whose activation mediates increase in intracellular calcium transients (Di Giorgi Gerevini et al, 2004;Platel et al, 2008aPlatel et al, , 2008b. Moreover, expression of functional NMDA receptors has been recently recorded in neuroblasts from the rostral part of the SVZ while no detectable currents have been identified in the more posterior SVZ along the lateral wall of the lateral ventricle nor in astrocytelike cells .…”

“…Indeed, young adult singlecell NR1 knock-out mice, in which the NMDAR subunit NR1, that is essential for NMDAR functionality, has been deleted in individual neuroblasts through SVZ electroporation, do not show any difference in the speed of neuroblast migration . Conversely, antagonistmediated inhibition of Glu K5 -containing kainate receptor but not of the metabotropic mGluR5 receptor, increases the speed of neuronal migration (Platel et al, 2008b). Using time-lapse confocal microscopy on fluorescently labeled neuroblasts in acute brain slices (Bovetti et al, 2007a;Bovetti et al, 2007b;De Marchis S. et al, 2001), we also analyzed the involvement of GABA and glutamate receptors in neuroblast tangential migration along the RMS, both in early postnatal period (P5, when chain migration does not occur yet) and in young-adult mice (P21) when glial tube are formed .…”

Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain

“…mGluRs and kainate receptors have been observed on neuroblasts in the SVZ (Di Giorgi-Gerevini et al, 2005;Platel et al, 2008;Platel et al, 2010). The origin of glutamate appears to be the subventricular astrocytes, in which vesicular glutamate transporter 1 is expressed (Platel et al, 2010).…”

Rôle des récepteurs NMDA et du glutamate astrocytaire dans la neurogenèse postnatale

“…Au niveau de la ZSV, la signalisation glutamatergique semblait n'apparaître que très tardivement, une fois les cellules sur le point de s'intégrer dans le bulbe olfactif. Néanmoins nos études précédentes démontraient la présence et la fonctionnalité d'autres récepteurs au glutamate durant la migration rostrale [3]. Nous avons donc entrepris de caractériser plus en détails l'apparition des récepteurs NMDA, la source du glutamate qui les active ainsi que le rôle de ces récepteurs en utilisant la technique knock-out sur cellule unique in vivo [4].…”