Synapse regeneration and signals for directed axonal growth in the central nervous system of the leech

In each segmental ganglion of the leech there is one S interneuron which extends an axon anteriorly and posteriorly halfway along the connectives to make electrical synapses exclusively with the tips of the next S-cell axons. Fluorescent dyes of low molecular weight such as Lucifer Yellow [Stewart, W. W. (1978).Cell14, 741-759] pass selectively from one S-cell axon to the next. An S-cell axon that has been severed regenerates along its distal stump to synapse with its usual target, the adjacent S-cell axon [Muller, K. J., and Carbonetto, S. T. (1979).J. Comp. Neurol.185, 485-516]. In experiments reported here, Lucifer Yellow injected into a regenerated S cell passes exclusively into the target S cell, indicating that the injured cell regenerates a synapse specifically with its usual target. When the target of a severed S-cell axon is selectively eliminated by the intracellular injection of protease, the severed axon regenerates along its distal stump in a normal fashion, stopping at the usual site of synapse without making detectable alternative connections. Similarly, intact S cells are apparently unaffected by the protease killing of their target; they neither grow nor retract and form no aberrant synapses. In contrast, when its target is killed, an intact axon can be triggered to sprout at its tip by injuring another branch of the same cell. The sprouted axons grow along the pathway formerly occupied by the killed cell and make no detectable synapses. It appears that cellular injury turns on general growth processes within the neuron that are expressed only by axonal branches that have lost contact with their target.