Effects of thyroid hormone on synaptogenesis in the molecular layer of the developing rat cerebellum.

In 14-day-old thyroid-deficient rats, qualitative and quantitative ultrastructural study of the cerebellar molecular layer shows that the retardation in synaptogenesis between Purkinje cell dendritic spines or excrescences and synaptic segments of parallel fibres is related to the marked hypoplasia of Purkinje cell dendritic arborizations and to the retarded development of parallel fibres rather than to the delay in the deposition of granule cells. Synaptogenesis inhibition is more marked in the inner parts of the molecular layer so that the normal "march" of synaptogenesis from the bottom of the layer upwards is distorted. This study also indicates that thyroid hormone deprivation affects synaptogenesis by interacting with growth and branching of neuronal processes and with the organization of their microtubular apparatus rather than with the differentiation of the structural specializations forming the synapses. The first corrective effect of a very low dose of thyroxine administered 24 h before sacrifice to the hypothyroid animal is observed at the level of parallel fibres and their varicosities. Purkinje cells take longer to respond to the hormone. However, their directing role in the histogenesis of the cerebellar cortex is strongly suggested. The significance of these observations with regard to the mechanisms underlying the effects of thyroid hormone on synaptogenesis and synaptic organization between Purkinje cells and parallel fibres as well as on histogenetic granule cell death is discussed.