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Transmission blockade during neuronal development

Observations on the trochlear nucleus with quantitative histological methods and with ultrastructural and axonal transport studies in the chick embryo

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Summary

Transmission blockade has been performed with α- and β-bungarotoxin and with d-tubocurarine in ten to eighteen-day-old chick embryos. Prevention of the naturally occurring nerve cell death in the trochlear nucleus after postsynaptic blockade is reported. Using stereological and biomathematical methods, it was possible to describe an absolute enlargement in volume of the trochlear nucleus despite a significant overall decrease in brain weight after α-bungarotoxin and d-tubocurarine treatment. Nuclear and nucleolar diameters and the number of nucleoli per cell nucleus in trochlear neurons show time-dependent changes, but not differences between the controls and curare treated chick embryos. The ultrastructural appearance of trochlear neurons is not different between the controls and curare treated embryos after eight days of transmission blockade, indicating a similar maturation in these two groups. Only a somewhat higher frequency of dense bodies has been found after curare treatment. In contrast to these findings, the electron micrographs of β-bungarotoxin treated chick embryos show severe degenerative signs in the trochlear nucleus and other motor brain regions very similar to the morphological changes after axonal lesions (retrograde axonal reaction). The quantitative Golgi-analysis of trochlear neurons demonstrates a significant decrease in dendritic branching after curare treatment. All neurons in the trochlear nucleus are labeled by retrograde transport of horseradish-peroxidase after injection into the upper extraocular muscles both in the controls and curare-treated animals. Therefore, we can assume that the motor neurons have maintained contacts with their peripheral target even after eight days of transmission blockade.

Comparing biochemical and pharmacological data published in the literature with our present results, we conclude that an increased number of acetylcholine receptors in the peripheral target represents the cellular basis for the prevention of the naturally occurring neuronal cell death in neuromuscular systems. Therefore, the quantitative relations between neurons and post-synaptic receptor sites may be one of the important factors in the development and maintenance of neuromuscular systems.

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Zilles, K., Becker, CM. & Schleicher, A. Transmission blockade during neuronal development. Anat Embryol 163, 87–123 (1981). https://doi.org/10.1007/BF00315773

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