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 following freeze lesioning of the newborn neocortex. After a survival time of 3 months, a small area of dysplastic cortex surrounded by histologically normal (exofocal) neocortex was observed. The dysplastic cortex is characterized by the formation of a small sulcus and a three- to four-layered architecture. Two questions are addressed here: (i) is the hyperexcitability associated with changes in binding to major excitatory and inhibitory transmitter receptors in the dysplastic cortex?; and (ii) do such changes also occur in the exofocal cortex? Alterations in binding to glutamatergic N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and GABA(A) and GABA(B) (gamma-aminobutyric acid) receptors are demonstrated with quantitative in vitro receptor autoradiography by using the ligands [3H]MK-801, [3H]AMPA, [3H]kainate, [3H]muscimol and [3H]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 lesioned hemisphere show an imbalance between excitatory and inhibitory receptor 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) and NMDA receptors is not significantly changed in the exofocal areas. The 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 with migration disorders.
Zilles
K
K
C. & O. Vogt Institute of Brain Research, University of Düsseldorf, Germany. zilles@hirn.uni-duesseldorf.de
Qü
M
M
Schleicher
A
A
Luhmann
H J
HJ
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001665:Binding Sites; D002465:Cell Movement / Q000502:physiology; D003452:Cryosurgery; D008953:Models, Anatomic; D008959:Models, Neurological; D019579:Neocortex / Q000737:chemistry* / Q000254:growth & development / Q000473:pathology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis*; D018080:Receptors, GABA-B / Q000032:analysis*; D018092:Kainic Acid Receptors / Q000032:analysis*; D000097806:GluK2 Kainate Receptor
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor