Sprouting of active nerve terminals in partially inactive muscles of the rat

1. Certain muscles in the hind foot of rats were partially paralysed by applying tetrodotoxin to part of their motor innervation. In these muscles motor nerve sprouting occurred from the terminals of the unblocked axons. The extent of sprouting was compared with that seen in totally paralysed and in partially denervated muscles. 2. Action potentials were blocked in the medial and lateral plantar nerves of adult rats for 5-13 days by continuous superfusion with a solution containing tetrodotoxin. The drug was delivered through a tube and nerve cuff from an osmotic pump placed intraperitoneally. Control experiments showed that nerve block was complete and that signs of nerve damage were absent in the animals included in the study. 3. Two muscles (the second lumbrical and flexor digitorum brevis), which received innervation only from the medial plantar nerve, were totally paralysed by the nerve block. Two different muscles (the fourth lumbrical and flexor digitorum quinti brevis) were only partially paralysed, since they received their innervation from the lateral plantar nerve and, in addition, from the sural nerve which was not blocked. One day before the final experiment, the lateral plantar nerve was cut, and its terminals degenerated. Thus in the partially paralysed muscles only the unblocked terminals from the sural nerve remained. These terminals were observed after staining with zinc iodide and osmium tetroxide. Similarly, terminals from the medial plantar nerve were examined in the totally blocked muscles from the same animal. 4. In other experiments, muscles were partially denervated by cutting the lateral plantar nerve in order to compare effects of nerve block and nerve section. 5. Sprouting occurred under all three conditions. Active terminals in the muscles partially paralysed for 5-7 days sprouted to the same extent as terminals in muscles totally blocked during the same period: about 35% of the terminals had sprouts, and their average length was about 13 micron. Sprouting was more pronounced in partially denervated muscles: about 65% of the terminals had sprouts and they averaged 24 micron in length. Collateral (preterminal) sprouts were seen only after partial denervation. 6. Physiological and histological observations suggested that sprouts in paralysed muscles, unlike those in partially denervated muscles, seldom if ever made new synapses on neighbouring muscle fibres, even after 12-13 days of nerve block. 7. The results show that inactive muscle fibres cause active nerve terminals on neighbouring fibres to sprout, perhaps by releasing a diffusible, sprout-promoting factor, which is part of the stimulus for motor nerve sprouting in partially denervated muscles.