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

Nature volume 406, pages 726–731 (2000)Cite this article

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 terminals1,2. 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 debate3,4,5,6. 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.

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Figure 1: Generation of Emx1-Cre mice and their cortex-restricted recombination.
Figure 2: Cortex-restricted NR1 disruption in CxNR1KO mice.
Figure 3: Lack of NMDAR-mediated excitation in barrel cortex of CxNR1KO mice.
Figure 4: Whisker-related patterns as revealed by cytochrome oxidase histochemistry.
Figure 5: Partial thalamocortical axonal patterns, absence of barrels and barrel boundaries.

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Acknowledgements

We thank D. Gerber for critical reading; M. Yoshida and S. Aizawa for information and a probe of Emx1 gene; J. Tsien, Y. Li, J.-i. Miyazaki and A. Nagy for NR1flox/flox, NR1+/-, CAG-CAT-Z and CMV-Cre mice, respectively; C. Lovett for Cre/LacZ PCR primers; K. Crossin for tenascin antibody; M. Tanaka, H. Gomi, A. Kato, K. Ishii, T. Ikeda and H. Kanki for advice in experiments/manuscript preparation; T. A. Woolsey for helpful discussion; and N. Yoshida, Y. Onodera, R. Ando and R. Nomura for technical assistance. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (T.I.), by the Whitehall Foundation and the NIH/NINDS (R.S.E.) and by the NIH (S.T.).

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Authors and Affiliations

  1. Laboratory for Behavioral Genetics, Brain Science Institute (BSI), RIKEN, 2-1 Hirosawa, Wako-shi, 351-0198, Saitama, Japan

    Takuji Iwasato, Hiroshi Nishiyama, Yusuke Taguchi & Shigeyoshi Itohara

  2. Department of Cell Biology and Anatomy and Neuroscience Center, LSUHSC, New Orleans, 70112, Louisiana , USA

    Akash Datwani & Reha S. Erzurumlu

  3. Laboratory for Neuronal Circuit Dynamics, Brain Science Institute (BSI), RIKEN, 2-1 Hirosawa, Wako-shi, 351-0198, Saitama, Japan

    Alexander M. Wolf & Thomas Knöpfel

  4. Institute for Virus Research, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan

    Hiroshi Nishiyama

  5. RIKEN-MIT Neuroscience Research Center Department of Biology, Howard Hughes Medical Institute Center for Learning & Memory, MIT, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Susumu Tonegawa

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  1. Takuji Iwasato
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Correspondence to Shigeyoshi Itohara.

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Iwasato, T., Datwani, A., Wolf, A. et al. Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature 406, 726–731 (2000). https://doi.org/10.1038/35021059

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