CHARACTERIZATION OF NEURONAL MIGRATION DISORDERS IN NEOCORTICAL STRUCTURES - QUANTITATIVE RECEPTOR AUTORADIOGRAPHY OF IONOTROPIC GLUTAMATE,GABA(A), AND GABA(B) RECEPTORS

Epileptiform activity was previously described [Luhmann et al. (1998) Eur.J. Neurosci., 10, 3085-3094] in the neocortex of the adult rat fol lowing freeze lesioning of the newborn neocortex. After a survival tim e of 3 months, a small area of dysplastic cortex surrounded by histolo gically normal (exofocal) neocortex was observed. The dysplastic corte x is characterized by the formation of a small sulcus and a three- to four-layered architecture. Two questions are addressed here: (i) is th e hyperexcitability associated with changes in binding to major excita tory and inhibitory transmitter receptors in the dysplastic cortex?; a nd (ii) do such changes also occur in the exofocal cortex? Alterations in binding to glutamatergic N-methyl-D-aspartate (NMDA), lpha-amino-3 -hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and GABA(A ) and GABA(B) (gamma-aminobutyric acid) receptors are demonstrated wit h quantitative in vitro receptor autoradiography by using the ligands [H-3]MK-801, [H-3]AMPA, [H-3]kainate, [H-3]muscimol and [H-3]baclofen, respectively. In the dysplastic cortex, the binding to NMDA, AMPA and kainate receptors is significantly increased, whereas the binding to GABA(A) and GABA(B) receptors is reduced. Exofocal areas of the lesion ed hemisphere show an imbalance between excitatory and inhibitory rece ptor binding with an up-regulation of the binding to AMPA and kainate, and a down-regulation to GABA(A) receptors. The binding to GABA(B) an d NMDA receptors is not significantly changed in the exofocal areas. T he imbalance between excitatory and inhibitory receptors may cause the hyperexcitability, as previously found in the identical experimental model, and may also induce epileptiform activity in the human cortex w ith migration disorders.