Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits.
N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week. Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals. Therefore, cerebellar NR2A is important for proper motor coordination and cannot be replaced by long-term expression of NR2B. Consequently, the physiological exchange of NMDA receptor subunits during cerebellar granule cell maturation is important for accurate postnatal development and function.
Schlett
Katalin
K
Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
Pieri
Isabelle
I
Metzger
Friedrich
F
Marchetti
Lara
L
Steigerwald
Frank
F
Dere
Ekrem
E
Kirilly
Dániel
D
Tárnok
Krisztián
K
Barabás
Brigitta
B
Varga
Agnes Kis
AK
Gerspach
Jeannette
J
Huston
Josephp
J
Pfizenmaier
Klaus
K
Köhr
Georg
G
Eisel
Ulrich L M
UL
D000818:Animals; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019957:Motor Skills Disorders / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D013995:Time
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate