NMDA receptor-dependent regulation of axonal and dendritic branching.
In the rodent trigeminal principal nucleus (PrV), trigeminal afferent terminals and postsynaptic cells form discrete modules ("barrelettes") that replicate the patterned array of whiskers and sinus hairs on the snout. Barrelette neurons of the PrV relay whisker-specific patterns to the contralateral thalamus and, subsequently, to the primary somatosensory barrel cortex. Genetic impairment of NMDA receptor (NMDAR) function blocks development of barrelettes in the PrV. Underlying cellular and functional defects are not known. Here, we examined morphological differentiation of whisker afferents, dendritic differentiation of barrelette cells, and their electrophysiological properties in mice with genetic perturbations of the essential subunit NR1 of NMDARs. We show that in NR1 gene knock-down (KD) and knock-out mice, whisker afferents begin their embryonic development normally but, over time, fail to segregate into patches, and instead they develop exuberant terminal arbors spanning most of the PrV. Postnatal NR1KD barrelette cells, with significantly reduced NMDA currents, retain their membrane and synaptic properties but develop longer dendrites with no orientation preference. These results indicate that NMDARs regulate growth of presynaptic terminal arbors and postsynaptic dendritic branching, thereby leading to consolidation of synapses and patterning of presynaptic and postsynaptic elements.
Lee
Li-Jen
LJ
Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Lo
Fu-Sun
FS
Erzurumlu
Reha S
RS
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001640:Bicuculline / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D004347:Drug Interactions; D003576:Electron Transport Complex IV / Q000378:metabolism; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000502:physiology*; D016622:Silver Staining / Q000379:methods; D014278:Trigeminal Nuclei / Q000166:cytology*; D014738:Vibrissae / Q000166:cytology / Q000254:growth & development / Q000294:innervation
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; C409466:NR1 NMDA receptor; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; D003576:Electron Transport Complex IV; D001640:Bicuculline
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