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During development, the survival of neurons in the CNS depends critically on interactions with postsynaptic target cells. The role of target cells on the maintenance of afferent neurons in the adult, however, is a matter of controversy. Morphological alterations of target-deprived neurons, such as axonal retraction or pruning, may occur. We have therefore undertaken an analysis of target-deprived neurons over time after an excitotoxic lesion in order to investigate these potential changes. Dorsal column nuclei (DCN) neurons were deprived of their target neurons in adult rats by the injection of kainic acid into the ventrobasal thalamic complex. Anterogradely transported wheat germ agglutinin conjugated to HRP from the DCN showed a progressive decrease of the density of afferent terminals during the first month after lesion. Density stabilized thereafter through the longest time studied (8 months). In contrast, the extent of the area occupied by DCN projections did not change up to 1 month and then shrank over time. These results indicated a continuous decrease in the number of axonal elements in the lesion, which is the strongest during the first month postlesion. To interpret these data, we then studied axonal morphology. Diffusion-filled lemniscal axons were labeled by WGA- HRP injections aimed at the medial lemniscus. There was no conspicuous alteration of axonal stems in the medial lemniscus. Terminal axonal arborizations and swellings dramatically decreased in number over the first month after the kainate injection, and large axonal varicosities were formed over the same period of time. These morphological data suggest that the decrease in number of axons in an excitotoxic lesion is related, at least during the first month, to a loss of axonal terminal arborizations rather than to a retraction of axonal stems. The pattern of terminal arborizations in the adult CNS may therefore depend critically on interactions of afferents with their target neurons, while the maintenance of the axonal stems does not.

Target dependence of adult neurons: pattern of terminal arborizations