Denervation-induced collateral sprouting: no case for tracing methods

Sprouting of axonal collaterals is assumed to represent a major feature of the regenerative capacity of the CNS. Following the denervation of a brain region, synaptic contact sites become free and are replaced by sprouted collaterals of intact afferents of this area. During the last three years, numerous studies have been published which have used anatomical tracing methods to demonstrate this morphological consequence of lesions. This paper criticizes the use of tracing methods in this research field because of the striking problems in quantifying the altered connectivity of a denervated structure. This critique is illustrated by summarizing the studies on the lesion-induced morphological effects within the nigro-striatal system which has become a paradigmatic neuronal circuit for the study of neuronal and functional reorganization. It is concluded that anatomical tracing methods seem to be inappropriate in studying denervation-induced collateral sprouting.