Alteration of mouse cerebellar circuits following methylazoxymethanol treatment during development: immunohistochemistry of GABAergic elements and electron microscopic study.

Methylazoxymethanol (MAM) injected postnatally affects cerebellar development in mice. A single injection at the fifth postnatal day produces hypogranular cerebella whereas a single injection at birth produces, in addition, a disorderly cytoarchitecture of the folium and alteration of Purkinje cell positioning (Bejar et al.: Exp. Brain Res. 57:279-285, '85). In the present study we have used immunohistochemistry with anti-GABA immune serum and electron microscopy to further characterize these alterations. In addition to the already-described nonoccupied dendritic spines of Purkinje cells both in mice injected the day of birth and or at the fifth postnatal day, we have observed, in animals injected at birth, the absence of pericellular baskets around Purkinje cells and the presence of heterologous synapses between mossy fibres and Purkinje cell dendrites. These heterologous synapses apparently disappear after postnatal day 20. By using an appropriate timing of MAM injection, different types of hypogranular cerebella, phenocopies of different mutants, can be obtained in large enough number to carry out extensive biochemical studies at each developmental age.