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Cerebral Cortex Advance Access originally published online on July 21, 2004
Cerebral Cortex 2005 15(3):349-358; doi:10.1093/cercor/bhh137
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Cerebral Cortex V 15 N 3 © Oxford University Press 2004; all rights reserved

Neonatal NMDA Receptor Blockade Disturbs Neuronal Migration in Rat Somatosensory Cortex In Vivo

Petra Reiprich1, Werner Kilb2 and Heiko J. Luhmann2

1 Institute for Medicine, Research Center Jülich, Jülich, Germany and 2 Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany

Address correspondence to Heiko J. Luhmann, Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55128 Mainz, Germany. Email: luhmann{at}uni-mainz.de.

Glutamate plays an important role in the control of neuronal migration in the developing cerebral cortex. The present study describes changes in the structure and function of the cerebral cortex after transient blockade of N-methyl-D-aspartate (NMDA) receptors during the late period of neuronal migration. Elvax slices containing the NMDA antagonist MK801 were placed over the somatosensory cortex of newborn rats and the drug was released over a period of 2–3 days. After survival times of 1 or 2 weeks, neuroanatomical and in vitro electrophysiological analyses revealed prominent structural and functional alterations in the cortical region underlying the implant. Cortical lamination was disturbed and heterotopic cell clusters were found in layer I of MK801-treated animals. Morphologically identified pyramidal neurons recorded in MK801-treated cortex revealed late NMDA receptor-mediated synaptic inputs and fragile monosynaptic responses at stimulation frequencies >0.2 Hz. Our data indicate that impairment of NMDA receptors during early corticogenesis induces neuronal migration disorders and delays the functional maturation of the developing cortical network.

Key Words: heterotopia • maturation • neonatal • pyramidal neurons • synaptic responses


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