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The Journal of Neuroscience, October 1, 2008, 28(40):9953-9968; doi:10.1523/JNEUROSCI.0880-08.2008

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Development/Plasticity/Repair
Role of GluR1 in Activity-Dependent Motor System Development

Lei Zhang,¹ Joachim Schessl,¹ Markus Werner,² Carsten Bonnemann,¹ Guoxiang Xiong,¹ Jelena Mojsilovic-Petrovic,¹ Weiguo Zhou,¹ Akiva Cohen,¹ Peter Seeburg,³ Hidemi Misawa,⁴ Aditi Jayaram,⁵ Kirkwood Personius,⁵ Michael Hollmann,² Rolf Sprengel,³ and Robert Kalb¹

¹Department of Pediatrics, Division of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, ²Department of Biochemistry I, Receptor Biochemistry, Ruhr University Bochum, D-44780 Bochum, Germany, ³Max-Planck-Institut für medizinische Forschung, D-69120 Heidelberg, Germany, ⁴Department of Pharmacology, Keio University, Minato-ku, Tokyo 105-8512, Japan, and ⁵Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, New York 14214-3079

Correspondence should be addressed to Dr. Robert Kalb, Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104. Email: kalb{at}email.chop.edu

Activity-dependent specification of neuronal architecture during early postnatal life is essential for refining the precision of communication between neurons. In the spinal cord under normal circumstances, the AMPA receptor subunit GluR1 is expressed at high levels by motor neurons and surrounding interneurons during this critical developmental period, although the role it plays in circuit formation and locomotor behavior is unknown. Here, we show that GluR1 promotes dendrite growth in a non-cell-autonomous manner in vitro and in vivo. The mal-development of motor neuron dendrites is associated with changes in the pattern of interneuronal connectivity within the segmental spinal cord and defects in strength and endurance. Transgenic expression of GluR1 in adult motor neurons leads to dendrite remodeling and supernormal locomotor function. GluR1 expression by neurons within the segmental spinal cord plays an essential role in formation of the neural network that underlies normal motor behavior.

Key words: motor neurons; spinal cord; synaptic activity; motor behavior; glutamate receptors; network activity

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Received July 24, 2008; accepted Aug. 18, 2008.

Correspondence should be addressed to Dr. Robert Kalb, Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104. Email: kalb{at}email.chop.edu

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