INTRINSIC NEURONAL DETERMINANTS LOCALLY REGULATE EXTRASYNAPTIC AND SYNAPTIC GROWTH AT THE ADULT NEUROMUSCULAR-JUNCTION

Long-term functional plasticity in the nervous system can involve stru ctural changes in terminal arborization and synaptic connections, To d etermine whether the differential expression of intrinsic neuronal det erminants affects structural plasticity, we produced and analyzed tran sgenic mice overexpressing the cytosolic proteins cortical cytoskeleto n-associated protein 23 (CAP-23) and growth-associated protein 43 (GAP -43) in adult neurons. Like GAP-43, CAP-23 was downregulated in mouse motor nerves and neuromuscular junctions during the second postnatal w eek and reexpressed during regeneration, In transgenic mice, the expre ssion of either protein in adult motoneurons induced spontaneous and g reatly potentiated stimulus-induced nerve sprouting at the neuromuscul ar junction, This sprouting had transgene-specific features, with CAP- 23 inducing longer, but less numerous sprouts than GAP-43, Crossing of the transgenic mice led to dramatic potentiation of the sprout-induci ng activities of GAP-43 and CAP-23, indicating that these related prot eins have complementary and synergistic activities, In addition to ult raterminal sprouting, substantial growth of synaptic structures was in duced. Experiments with pre- and postsynaptic toxins revealed that in the presence of GAP-43 or CAP-23, sprouting was stimulated by a mechan ism that responds to reduced transmitter release and may be independen t of postsynaptic activation, These results demonstrate the importance of intrinsic determinants in structural plasticity and provide an exp erimental approach to study its role in nervous system function.