AUTORADIOGRAPHIC LOCALIZATION OF [H-3] L-GLUTAMATE BINDING-SITES IN AMODEL OF CEREBELLAR GRANULE CELL ECTOPIA GENERATED BY METHYLAZOXYMETHANOL TREATMENT

The distribution of [H-3]glutamate binding sites was studied in a mode l of altered cerebellar development obtained by injecting methylazoxym ethanol (MAM) in 5-day-old mice. In these mice. at the 25th postnatal day, cerebella were smaller than normal, stratification was normal exc ept for the presence in some lobes of a thin ectopic granule cell laye r in the middle of the molecular layer, the proportion of the distribu tion of [H-3]glutamate binding sites between molecular and internal gr anule cell layers was maintained but site density of both quisqualate- and NMDA-sensitive types was increased in the two layers. In the mole cular layer, this increase was uniform in spite of the presence of the ectopic cell layer. In the internal granular layer, the increase of q uisqualate-sensitive and NMDA-sensitive [H-3]glutamate binding sites i s topographically segregated and the first corresponds to areas of les ser cellular density. These results show that MAM treatment induces pe rsistent alterations of the cerebellar glutamatergic system, which con sist of receptor over-expression, possibly due to deficit of innervati on, reactive gliosis and immaturity of surviving granule cells.