NMDA receptor NR2B subunit over-expression increases cerebellar granule cell migratory activity

J Neurochem. 2008 Feb;104(3):818-29. doi: 10.1111/j.1471-4159.2007.05051.x. Epub 2007 Nov 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • Calcium / metabolism
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cerebellum / cytology*
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression Regulation / physiology*
  • Growth Cones / drug effects
  • Growth Cones / physiology
  • Mice
  • Mice, Knockout
  • Microscopy, Video / methods
  • Mutation / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Receptors, N-Methyl-D-Aspartate / deficiency
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • Excitatory Amino Acid Antagonists
  • NR2B NMDA receptor
  • NR2C NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Bromodeoxyuridine
  • Calcium