The effects of increasing neural activity on sprouting remain unclear and c
ontroversial. In a rat model of partial denervation of skeletal muscles, we
investigated the effect of neuromuscular activity on sprouting. Rat hindli
mb muscles were partially denervated by avulsion of either L4 or L5 spinal
root. Immediately after partial denervation, the rats were divided into thr
ee groups: (1) normal caged activity, (2) running exercise on wheels, 8 hr
daily, and (3) functional electrical stimulation (FES) of sciatic nerves, 2
0 Hz for 8 hr daily. At 1 month, muscle unit (MU) enlargement was quantitat
ed electrophysiologically and histochemically. MU twitch force was increase
d by four- to fivefold by partial denervation in extensively denervated tib
ialis anterior (TA) and medial gastrocnemius (MG) and by approximately twof
old in moderately denervated plantaris (PL) and soleus (SOL). For the exten
sively denervated TA and MG muscles, MU enlargement, measured electrophysio
logically, declined significantly after an average of 1757 +/- 310 m/d runn
ing exercise and daily FES for 1 month. The detrimental effects on MU enlar
gement were much less but significant in the moderately denervated PL and d
id not reach statistical significance in the moderately denervated SOL musc
le. Histochemical evaluation of sprouting showed a reduction in the number
of sprouts in the extensively denervated TA muscle, but not the moderately
denervated PL and SOL muscles, by increased neuromuscular activity. Thus, i
ncreased neuromuscular activity is detrimental primarily in muscles that ar
e extensively denervated, and the MUs are smaller than under conditions in
which the muscles experience normal physiological levels of activation.