ARREST OF NEURONAL MIGRATION BY EXCITATORY AMINO-ACIDS IN HAMSTER DEVELOPING BRAIN

The influence of the excitotoxic cascade on the developing brain was i nvestigated using ibotenate, a glutamatergic agonist of both N-methyl- D-aspartate (NMDA) ionotropic receptors and metabotropic receptors. In jected in the neopallium of the golden hamster at the time of producti on of neurons normally destined for layers IV, III, and II, ibotenate induces arrests of migrating neurons at different distances from the g erminative zone within the radial migratory corridors, The resulting c ytoarchitectonic patterns include periventricular nodular heterotopias , subcortical band heterotopias, and intracortical arrests of migratin g neurons, The radial glial cells and the extracellular matrix are fre e of detectable damage that could suggest a defect in their guiding ro le. The migration disorders are prevented by coinjection of DL-2-amino -7-phosphoheptanoic acid, an NMDA ionotropic antagonist, but are not p revented by coinjection of L(+)-2-amino-3-phosphonopropionic acid, a m etabotropic antagonist, This implies that an excess of ionic influx th rough the NMDA channels of neurons alters the metabolic pathways suppo rting neuronal migration, Ibotenate, a unique molecular trigger of the excitotoxic cascade, produces a wide spectrum of abnormal neuronal mi gration patterns recognized in mammals, including the neocortical devi ations encountered in the human brain.