Cellular and axonal diversity in molecular layer heterotopia of the rat cerebellar vermis.

Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.

Neuronal migration defect of the developing cerebellar vermis in substrains of C57BL/6 mice: cytoarchitecture and prevalence of molecular layer heterotopia.

Abnormal development of the cerebellum is often associated with disorders of movement, postural control, and motor learning. Rodent models are widely used to study normal and abnormal cerebellar development and have revealed the roles of many important genetic and environmental factors. In the present report we describe the prevalence and cytoarchitecture of molecular-layer heterotopia, a malformation of neuronal migration, in the cerebellar vermis of C57BL/6 mice and closely-related strains. In particular, we found a diverse number of cell-types affected by these malformations including Purkinje cells, granule cells, inhibitory interneurons (GABAergic and glycinergic), and glia. Heterotopia were not observed in a sample of wild-derived mice, outbred mice, or inbred mice not closely related to C57BL/6 mice. These data are relevant to the use of C57BL/6 mice as models in the study of brain and behavior relationships and provide greater understanding of human cerebellar dysplasia.

Axonal anatomy of molecular layer heterotopia of the cerebellar vermis.

C57BL/6 mice and closely related strains exhibit heterotopia in the molecular layer of folia VIII and IX of the cerebellar vermis. Previously, we demonstrated that heterotopia are composed primarily of granule cells, Golgi cells, and GABAergic interneurons and are indicative of neuronal migration defect. In the present report we use immunocytochemistry and Thy1-YFP reporter mice to reveal the axonal constituents of cerebellar heterotopia which include mossy fibers, as well as serotonergic, cholinergic, and catecholaminergic axons. These data are relevant toward understanding of the mechanisms of axonal targeting during normal and abnormal cerebellar development.