The autoradiographic demonstration of axonal connections in the central nervous system.

Most of the published work on the phenomenon of axoplasmic transport has been directed towards determining the site of synthesis and the chemical nature of materials involved, the mechanisms responsible for their movement, and the rates at which they are transported (see refs. 1, 23, 44, 49, 53 for reviews). However, following the suggestion of Taylor and Weiss 68, several workers, notably Lasek et al. 45, have shown that the transport of radioactively labeled materials can be used to trace axonal connections autoradiographically. This approach has thus far been applied to the study of the central connections of certain peripherally located neurons (specifically the dorsal root ganglion cells 45, the ganglion cells of the retina 19,a°,aa,5°,65 and the olfactory receptorsT1). Although this method does not appear to have been used for tracing pathways arising and terminating within the central nervous system, it should be possible to do this by locally injecting radioactively labeled precursors of proteins or other macromolecules into the brain or spinal cord. Indeed, there are several reasons for thinking that this method may offer a number of advantages over other currently available techniques4L Nearly all experimental neuroanatomical techniques (including the various cell degeneration methods, the reduced silver techniques for impregnating degenerating axons such as the Nauta-Gygax method and its recent variants and the electron microscopic examination of degenerating axons and their terminals) are dependent upon a sequence of pathological changes following injury to the nervous system. This essential feature underlies a number of the problems encountered in the use and interpretation of these methods. Among the most significant difficulties is the fact that experimental lesions are usually non-specific, and destroy not only the neurons within the intended focus but also the fibers passing through that region and the axons terminating within it. Since degeneration inevitably alters the normal morphol-