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Journal of Neuroscience, Vol 15, 2040-2056, Copyright © 1995 by Society for Neuroscience
Target neuron controls the integrity of afferent axon phenotype: a study on the Purkinje cell-climbing fiber system in cerebellar mutant mice
F Rossi, A Jankovski and C Sotelo
INSERM U. 106, Hopital de la Salpetriere, Paris, France.
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.
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