title: NMDA receptor NR2B subunit over-expression increases cerebellar granule cell migratory activity.
abstract: Glutamate acting on NMDA receptors (NMDARs) is known to influence cerebellar granule cell migration. Subunit composition of NMDARs in granule cells changes characteristically during development: NR2B subunit containing receptors are abundant during migration towards the internal granule cell layer but are gradually replaced by NR2A and/or NR2C subunits once the final position is reached. Cerebellar granule cell migration was investigated using mutant mouse lines either with a deletion of the NR2C gene (NR2C(-/-) mice) or expressing NR2B instead of the NR2C subunit (NR2C-2B mice). BrdU-labeling revealed that over-expression of NR2B increased granule cell translocation in vivo, while the lack of NR2C subunit did not have any detectable effects on cell migration. Cellular composition of wild-type and mutant dissociated cerebellar granule cell cultures isolated from 10-day-old cerebella were similar, but NR2C-2B cultures had elevated level of NR2B subunits and intracellular Ca2+ imaging revealed higher sensitivity towards the addition of NR2B-selective antagonist in vitro. Time-lapse videomicroscopic observations revealed that average migratory velocity and the proportion of translocating cell bodies were significantly higher in NR2C-2B than in wild-type cultures. Our results provide evidence that NR2B-containing NMDARs can have specialized roles during granule cell migration and can increase migratory speed.
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Tárnok
authors.forename: Katalin
authors.initials: K
authors.lastname: Czöndör
authors.forename: Márta
authors.initials: M
authors.lastname: Jelitai
authors.forename: András
authors.initials: A
authors.lastname: Czirók
authors.forename: Katalin
authors.initials: K
authors.lastname: Schlett
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video / Q000379:methods; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D001973:Bromodeoxyuridine; D002118:Calcium