Ultrastructural Analysis of Catecholaminergic Innervation in Weaver and Normal Mouse Cerebellar Cortices

The noradrenergic innervation of the mouse cerebellum, which is known for its important modulatory function, was analyzed immunocytochemically with an antibody against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. In control mice, the labeled afferent fibers belong to fine, beaded axons diffusely distributed throughout the cerebellar cortex. None of the 160 analyzed axon terminals established synaptic junctions with apposed neuronal elements. Thus, the cerebellar noradrenergic innervation is of the nonjunctional modality. Seventy-five percent of the labeled varicosities were apposed to dendritic profiles belonging to Purkinje, granule, stellate, and basket cells, although Purkinje cell dendrites, including spines, were the most frequently found. These observations suggest that the modulatory function of noradrenergic afferent fibers is exerted through paracrine interactions. In the agranular cerebellar cortex of the weaver mutant mouse, the density of labeled fibers is greatly increased. However, despite the presence of innumerable free postsynaptic differentiations (mainly Purkinje cell dendritic spines), only 2 of 188 observed varicosities established synaptic junctions. Thus, in the absence of granule cells, the noradrenergic innervation does not evolve from nonjunctional to junctional innervation, as was the case for the cerebellar serotonergic system (Beaudet and Sotelo [1981] Brain Res. 206:305-329). This finding indicates that the axonal remodeling in granuloprival cerebella does not affect the noradrenergic afferent system. Therefore, the authors conclude that there is some degree of specificity in the formation of heterologous synapses during the axon remodeling process occurring in all agranular cerebella.