TARGET NEURON CONTROLS THE INTEGRITY OF AFFERENT AXON PHENOTYPE - A STUDY ON THE PURKINJE CELL-CLIMBING FIBER SYSTEM IN CEREBELLAR MUTANT MICE

The effects of target loss on adult axonal arbors were investigated by comparing the morphological changes of adult climbing fibers in several mutant mouse strains where Purkinje cells slowly degenerate (namely, Lurcher, nervous, Purkinje cell degeneration, and tambaleante), with those occurring after a fast Purkinje cell death induced by mechanical lesions of the adult mouse cerebellum. In each of the different mutations, Purkinje cells displayed distinctive structural modifications. However, a set of regressive changes common to all strains could be disclosed, mostly dendritic atrophy and a progressive axonal retraction with the hypertrophy of recurrent collaterals. Climbing fibers that contacted such degenerating neurons also showed abnormal morphological features, consisting in the presence of extensive perisomatic plexuses, whereas peridendritic branches were atrophic or absent. In Lurcher mice, target-deprived climbing fibers were strictly confined around the granular-molecular layer interface and never penetrated into the molecular layer. Similar terminal plexuses at the level of the former Purkinje cell layer were observed in the other mutants. However, in the latter cases, atrophic terminal arbors were also present in the molecular layer, being confined to the deep portions in nervous, while spanning its whole extent in Purkinje cell degeneration and tambaleante mice. Following mechanical lesions, atrophic target-deprived climbing fibers were exclusively located in the molecular layer. In addition, some of the Purkinje cells that survived after the injury displayed regressive modifications similar to those observed in mutant mice, and their climbing fibers were characterized by perisomatic plexuses. These results show that the normal relationship between the climbing fiber and its Purkinje cell is already disrupted during the slow degeneration of the target neuron. As a consequence, the phenotypic pattern of target-deprived climbing fibers reflects the preceding interactions with their postsynaptic neurons and it is determined by the onset time and progression rate of purkinje cell degeneration.