Anatomical, physiological and biochemical studies of the cerebellum from mutant mice. II. Morphological study of cerebellar cortical neurons and circuits in the weaver mouse

Abstract

The vermis of the homozygous weaver mice has been examined with Golgi and electron microscopic techniques. In addition to the findings already reported by previous authors 12,29, new cytological features concerning all the cerebellar neuronal types and the synaptic reorganization of the cerebellar circuitry are described. As in other agranular cerebella, Purkinje cells do not develop spiny branchlets and have a randomly oriented dendritic tree. By contrast, their thock dendritis are studded with spines; according to their size and shape these were classified into: (a) small stubby spines which are the normal postsynaptic targets for climbing fibers; (b) tertiary-like spines, most of which are free of axonal contacts; (c) dolichoderus spines; (d) branching spines; and (e) hypertrophic spines. The last 3 types do not exist in normal cerebellum. Postsynaptic-like differentiations are frequently undercoating the smooth surface of the Purkinje dendrites. As it happens in the case of the free spines, freepostsynaptic sites in the shafts of the dendrites develop an extracellular material similar to the material present in synaptic clefts. Basket and stellate cells also develop postsynaptic-like differentiations undercoating the somatic and dendritic plasma membranes. These free postsynaptic sites can reach a gigantic size, being longer than 3 μm in lenght. The rare postmigrative granule cells which persist in wv exhibit claw-endings not only at the dendritic terminal segments, but at the proximal dendritic stems as well. Some of these granule cells, besides having fully achieved migration, undergo a degenerative process indicating that they are probably directly affected by the mutation. Concerning the cerebellar circuitry, and despite the great number of free postsynaptic sites, the large majority of the synaptic contacts keep their specificity. However, some quantitative variations have been disclosed. The surface density of climbing varicosities is increases, whereas that of mossy rosettes is decreased. Stellate and basket fibers are present and their density is also decreased. Furthermore, the pinceau formation around the initial segment of the Purkinje cell axon is missing. In addition to all normal synaptic iccontacts (with the exception of the ‘parallel fiber-omnicellular system’) present in weaver, heterologous synapses have also been encountered, mainly concerning the Purkinje dendritic spines, which can be contacted by mossy rosettes, granule cell bodies and/or dendrites. Morphological signs of partial innervation of the free postsynaptic sites on the smooth surface of Purkinje dendrites and the perikarya and dendrites of interneurons have also been observed. These results confirm the existence of synaptic remodeling in wv cerebellum.