Genetic Dissection of Barrel Formation in the Rodent Somatosensory System

Takuji Iwasato

Abstract

In the rodent primary somatosensory cortex, the configuration of whiskers and sinus hairs on the snout is topographically represented as discrete modules of thalamocortical afferent (TCA) terminals and layer IV granule cells. Developed within the first week of life, these module (barrel) formations depend on neural activity from the peripheral sensory organs (e.g. whiskers). Although recognized as a good model of activity-dependent development of mammalian neuronal circuits, technical limitations have hindered our understanding of the underlying mechanisms of barrel formation.

We developed a conditional gene targeting system that can selectively manipulate specific genes in cortical excitatory neurons. Using this system, we generated cortex-restricted knockout mice (CxNR1KO) for NR1, an essential subunit of NMDA receptor. Patterning of TCAs (pre-synaptic pattern) in CxNR1KO mice is present but less distinct than in wild-type mice. Aggregates of layer IV neurons (post-synaptic pattern) do not develop. A detailed morphological analysis showed that the dendritic field of layer IV neurons failed to orient toward TCA terminal patches in these knockout mice. These results indicate that cortical NMDA receptor is a key player in both pre-synaptic and post-synaptic patterning in barrel formation.

Iwasato, T.+, Nomura, R., Ando, R., Ikeda, T., Tanaka, M and Itohara, S.+ Dorsal Telencephalon-Specific Expression of Cre Recombinase in PAC Transgenic Mice. Genesis 38, 130-138 (2004) + The corresponding authors

Datwani, A.*, Iwasato, T.*+, Itohara, S., and Erzurumlu, R.S.+, Lesion-induced thalamocortical axonal plasticity in the S1 cortex is independent of NMDA receptor function in excitatory cortical neurons. J. Neurosci. 22, 9171-9175 (2002). *The first two authors contributed equally to this work. +The corresponding authors

Iwasato, T., Datwani, A., Wolf, A.M., Nishiyama, H., Taguchi, Y., Tonegawa, S., Knšpfel, T., Erzurumlu, R.S. and Itohara, S. Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature 406, 726-731 (2000).

Iwasato, T., Erzurumlu, R.S., Chen, D.F., Huerta, P.T., Sasaoka, T., Ulupinar, E. and Tonegawa, S. NMDA receptor dependent refinement of somatosensory maps. Neuron 19, 1201-1210 (1997).

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