Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex

Nature. 2000 Aug 17;406(6797):726-31. doi: 10.1038/35021059.

Abstract

In the rodent primary somatosensory cortex, the configuration of whiskers and sinus hairs on the snout and of receptor-dense zones on the paws is topographically represented as discrete modules of layer IV granule cells (barrels) and thalamocortical afferent terminals. The role of neural activity, particularly activity mediated by NMDARs (N-methyl-D-aspartate receptors), in patterning of the somatosensory cortex has been a subject of debate. We have generated mice in which deletion of the NMDAR1 (NR1) gene is restricted to excitatory cortical neurons, and here we show that sensory periphery-related patterns develop normally in the brainstem and thalamic somatosensory relay stations of these mice. In the somatosensory cortex, thalamocortical afferents corresponding to large whiskers form patterns and display critical period plasticity, but their patterning is not as distinct as that seen in the cortex of normal mice. Other thalamocortical patterns corresponding to sinus hairs and digits are mostly absent. The cellular aggregates known as barrels and barrel boundaries do not develop even at sites where thalamocortical afferents cluster. Our findings indicate that cortical NMDARs are essential for the aggregation of layer IV cells into barrels and for development of the full complement of thalamocortical patterns.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Brain Stem / embryology
  • Cell Differentiation
  • Crosses, Genetic
  • Female
  • Homeodomain Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Pathways / embryology*
  • Neural Pathways / physiology
  • Neurons / physiology
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / embryology*
  • Somatosensory Cortex / physiology
  • Thalamus / embryology
  • Transcription Factors
  • Vibrissae / embryology

Substances

  • Homeodomain Proteins
  • NR1 NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Transcription Factors
  • empty spiracles homeobox proteins