NMDA receptor-dependent regulation of axonal and dendritic branching

J Neurosci. 2005 Mar 2;25(9):2304-11. doi: 10.1523/JNEUROSCI.4902-04.2005.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Axons / physiology*
  • Axons / ultrastructure
  • Bicuculline / pharmacology
  • Dendrites / physiology*
  • Dendrites / ultrastructure
  • Drug Interactions
  • Electron Transport Complex IV / metabolism
  • Embryo, Mammalian
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques / methods
  • Quinoxalines / pharmacology
  • Receptors, N-Methyl-D-Aspartate / deficiency
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Silver Staining / methods
  • Trigeminal Nuclei / cytology*
  • Vibrissae / cytology
  • Vibrissae / growth & development
  • Vibrissae / innervation

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • NR1 NMDA receptor
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • FG 9041
  • Electron Transport Complex IV
  • Bicuculline