BOTH BASIC FIBROBLAST GROWTH-FACTOR AND CILIARY NEUROTROPHIC FACTOR PROMOTE THE RETENTION OF POLYNEURONAL INNERVATION OF DEVELOPING SKELETAL-MUSCLE FIBERS

At birth, nearly all rat muscle fibers receive synaptic inputs from mo re than one motoneuron at a single end-plate site. By the end of the t hird postnatal week all but one of these inputs has been eliminated. D uring this loss of polyneuronal innervation, developing neuromuscular synapses compete with one another. Although the nature of this competi tion is not known, it is commonly assumed that it is mediated through differential activity of the competing inputs. One means by which such differential activity might be translated into a biological signal wo uld be if the synapses compete in an activity-dependent manner for a s carce supply of neurotrophic molecules. A prediction of this hypothesi s is that excess quantities of such trophic molecules will reduce comp etition and thereby slow down or abolish the normal loss of polyneuron al innervation. In newborn rats, the effects of injection of either ba sic fibroblast growth factor (bFGF) or ciliary neurotrophic factor (CN TF) on the outcome of neuromuscular synapse elimination were investiga ted. Daily injections of either bFGF or CNTF were made for 1 week into the lateral gastrocnemius muscle beginning at the postnatal age of 2 days. The amount of polyneuronal innervation of fibers in trophic mole cule-injected muscles and saline-injected contralateral muscles was as sayed using intracellular recording methods. For both bFGF- and CNTF-i njected muscles, an increase in the percentage of polyneuronally inner vated fibers relative to saline-injected muscles was noted. For bFGF-i njected muscles, the amount of polyneuronal innervation remained at ne arly 60% as late as the postnatal age of 14 days (P14). This is the am ount of polyneuronal innervation found at age 6 days in normal animals . Nearly 40% of the fibers of CNTF-injected muscles remained polyneuro nally innervated at age P14, the amount expected at age 9 days. These results indicate that both bFGF and CNTF exert powerful and long-lasti ng effects on developing neuromuscular synapses. (C) 1995 Academic Pre ss, Inc.