ABSTRACT
At the beginning of the twentieth century J.N.Langley and F.Tello made a series of studies on the reinnervation of denervated muscle and autonomic ganglia that were to establish principles of synapse formation that were not capitalised on for over 50 years. Tello (1907) showed that following muscle denervation by cutting a nerve, motor axons often grow down the empty Schwann cell tubes to enter the general region of the denervated synaptic sites of the muscle (Fig. 11.1A). Here the axons frequently branched profusely out of the enveloping Schwann tube to innervate the synaptic sites delineated by their characteristic endplate structure of a raised cytoplasm and concentration of nuclei (Fig. 11.1B). This indicated for the first time that although the branching axon had access to a large amount of muscle membrane it favoured terminal differentiation at the original synaptic site, suggesting that this site has a particular capacity for triggering the formation of terminals. Subsequently, Elsberg (1917) showed that adult muscle cells that possess an intact innervation resist additional innervation from another axon, emphasising that terminal formation appears to be restricted to synaptic sites that are not already occupied by synaptic terminals. The possibility that reinnervating axons may at least in some cases favour forming terminals on particular cells according to the segmental origins of the axons was raised by the experiments of Langley (1895). He showed that if the superior cervical ganglion was denervated by cutting the cervical sympathetic nerve trunk, subsequent reinnervation of the ganglion by each of the thoracic segmental nerves that contribute to the trunk is normal. In this case each axon comes to form synapses on the same ganglion cells that it previously innervated (Fig. 11.1C), providing evidence for the specificity of synapse formation, and leading Langley to conjecture that ‘at bottom then the phenomenon is a chemiotactic one’. At the beginning of the twentieth century, then, experiments had already been carried out indicating that the postsynaptic site contains information that can trigger terminal formation and that such sites may even distinguish between axons of different segmental origin. In the subsequent 50 years the tremendous stimulus to further research that might have been expected from the conceptual framework put in place by these experiments was not forthcoming. This chapter traces the historical development of how the work of Tello and Langley was taken up again in the latter half of the century, and of the progress made in identifying the molecules involved in the ‘chemiotatic’ process of terminal and synaptic site formation.
