Regeneration of axons and synaptic connections by touch sensory neurons in the leech central nervous system.

In studies of axonal regeneration, it has been difficult to determine (a) whether growth along the normal pathway is important for restoration of connections with previous targets and (b) whether the new synapses resemble the old in strength and location. To address these problems at the level of individual nerve cells, we have studied touch (T) sensory neurons in the leech after their axons have been severed and we have confirmed that their axons regenerate electrical connections with some of their usual synaptic targets in the central nervous system. Injections of horseradish peroxidase and Lucifer Yellow dye into separate T cells in unoperated animals showed that T cell axons typically run close to one another within single ganglia or from ganglion to ganglion. Knowledge of one T cell's arborizations thus revealed the groundplan of others in the same ganglia and the sites of apparent contact with its synaptic targets. For regenerating axons, those sprouts that encountered the normal pathway (as marked by homologous axons) grew preferentially along it. Despite the striking coincidence of old and new pathways, regenerated branching patterns within the ganglionic neuropils were usually incomplete and sometimes had atypical branches. Synaptic connections with normal targets (other T cells as well as S and C cells) were abnormally weak physiologically. The numbers of apparent contacts seen with the light microscope were also lower than normal. In addition, the strength of the synaptic potentials, normalized to the number of contacts (calculated as microvolts per contact), was generally smaller in the regenerated connections than in the controls, and smallest at earliest times, during the first 6 weeks following injury. It thus appears to be characteristic of T cell regeneration that axon regrowth is aided by the recognition of specific pathways and that successful regeneration, as assayed anatomically and physiologically, occurs frequently but usually incompletely.