 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, May 7, 2008, 28(19):4995-5006; doi:10.1523/JNEUROSCI.0861-08.2008
Previous Article | Next Article
Development/Plasticity/Repair
Glutamate Transporters Regulate Lesion-Induced Plasticity in the Developing Somatosensory Cortex
Chihiro Takasaki,1,2 Rieko Okada,1 Akira Mitani,3 Masahiro Fukaya,1 Miwako Yamasaki,1 Yuri Fujihara,1,2 Tetsuo Shirakawa,4 Kohichi Tanaka,5 andMasahiko Watanabe1 1Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, 2Department of Pediatric Dentistry, Hokkaido University School of Dentistry, Sapporo 060-8586, Japan, 3Cognitive Neuroscience, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan, 4Department of Pediatric Dentistry, Nihon University School of Dentistry, Tokyo 101-8310, Japan, and 5Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Correspondence should be addressed to Masahiko Watanabe, Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. Email: watamasa{at}med.hokudai.ac.jp
Glutamate transporters are involved in neural differentiation, neuronal survival, and synaptic transmission. In the present study, we examined glutamate transporter 1 (GLT1) expression in the neonatal somatosensory cortex of C57BL/6 mice, and pursued its role in somatosensory development by comparing barrel development between GLT1 knock-out and control mice. During the first few neonatal days, a critical period for barrels, GLT1 expression is strikingly upregulated in cortical astrocytes, whereas it was downregulated in neuronal elements to below the detection threshold. GLT1 knock-out neonates developed normally in terms of body growth, cortical histoarchitecture, barrel formation, and critical period termination. However, when row C whiskers were lesioned during the critical period, reduction of lesioned row C barrels and reciprocal expansion of intact row B/D barrels were both milder in GLT1 knock-out mice than in control littermates. Accordingly, the map plasticity index, calculated as (B + D)/2C, was significantly lowered in GLT1 knock-out mice. We also found that extracellular glutamate levels in the neonatal somatosensory cortex were significantly elevated in GLT1 knock-out mice. Diminished lesion-induced plasticity was further found in mutant mice lacking glutamate–aspartate transporter (GLAST), an astrocyte-specific glutamate transporter throughout development. Therefore, glutamate transporters regulate critical period plasticity by enhancing expansion of active barrels and shrinkage of inactive barrels. Because cortical contents of glutamate receptors and GLAST were unaltered in GLT1 knock-out mice, this action appears to be mediated, at least partly, by keeping the ambient glutamate level low. Considering an essential role of glutamate receptors in the formation of whisker-related thalamocortical synapse patterning, glutamate transporters thus facilitate their activity-dependent remodeling.
Key words: glutamate transporter; barrel; somatosensory; development; critical period; plasticity; mouse
Received Nov. 21, 2007; revised March 30, 2008; accepted April 8, 2008.
Correspondence should be addressed to Masahiko Watanabe, Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. Email: watamasa{at}med.hokudai.ac.jp
|
|
|
|
 |
|