Differential loss of neuromuscular connections according to activity level and spinal position of neonatal rabbit soleus motor neurons

Abstract

We have tested whether the ability of synapses to compete for occupancy of endplates during neuromuscular synapse elimination is affected by differences in the spinal position or in the activity level of the parent motor neuron. To test the role of spinal position, the relative sizes of motor units for motor neurons from middle and extreme (rostral/caudal) positions in the rabbit soleus motor pool were determined at 3 postnatal ages: 4–5 d (“early” ages, when the soleus is heavily polyinnervated), 8–9 d (“intermediate”), and 11–s15 d (“late,” when the soleus has just reached singly innervated state). Average motor unit sizes from extreme ventral roots were similar to those from middle ventral roots in early-aged soleus muscles but were significantly smaller (by 18–27%) for both intermediate and late muscles. Thus, motor neurons from extreme positions evidently compete less effectively for retention of synapses than those from middle positions. To test the role of differential activity, inactive and active synapses were pitted directly against one another by implanting Silastic plugs laden with tetrodotoxin (TTX) into one of the spinal nerves containing a minority of the soleus motor axons. Differential activity was maintained during a period of extensive synapse loss, from the time of the implant at day 4 or 5 until the intermediate age (day 8– 9). Motor unit twitch tensions were subsequently measured to determine the relative number of synapses retained by individual active and inactive motor neurons. The inactivated motor units were on average significantly larger (by more than 50%) than the corresponding group from normal and control-implanted animals. The abnormally large size of inactivated motor units persisted in animals allowed to recover from the TTX block and examined after multiple innervation had disappeared. Hence, the effect of the TTX block cannot be attributed to a simple slowing of synapse elimination specifically among the inactive motor neurons. We conclude that complete presynaptic inactivity improves the chances of survival relative to that for normal activity during synapse elimination in the neonatal rabbit soleus muscle. This difference in competitive ability may contribute to the development of an important characteristic of adult muscles, the correlation between motor unit size and recruitment threshold.

Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice

“…Conversely, reducing proprioceptive inputs to motoneurons (Benoit and Changeux 1975) or reducing inputs to muscle fibers by partial axotomy (Brown et al 1976) delays the elimination of poly-innervation. As a result, motor units whose activity was reduced by TTX had larger territories than those whose axons remained active (Callaway et al 1989). This was further supported by experimental and theoretical works suggesting that motoneurons with less active neuromuscular junctions have larger motor units than motoneurons with more active ones (Barber and Lichtman 1999;Callaway et al 1987;Nowik et al 2012).…”

Brain-derived neurotrophic factor transiently stabilizes silent synapses on developing neuromuscular junctions

“…Indeed, a few groups have reported that this underestimation can be quite large and significant (Taxt, 1983;Herrera, 1984). Most studies, however, report very close correlation between histologically determined and electrophysiologically determined percentages of multiply innervated fibers ( O'Brien et al, 1978;Betz et al, 1979;Brown et al, 1981Brown et al, , 1982Callaway et al, 1989). In previous studies from our laboratory with other growth factors such as LIF, we found no discrepancy between histological and electrophysiological assays of multiple innervation in treated muscles (Kwon et al, 1995).…”

Hormonal regulation of motor unit size and synaptic strength during synapse elimination in the rat levator ani muscle

“…Because the degree of synapse loss may be influenced by the position of the motor axons along the neural axis (Brown and Booth, 1983;Bennett and Lavidis, 1984a,b;Callaway et al, 1989), we compared the mean twitch size of LA motor units located in L5 to the mean twitch size of LA motor units in L6 during the period of synapse elimination. We found no evidence for a differential loss of synapses based on segmental location (L5 vs. L6), nor did we find evidence that androgen acted to spare more LA synapses in one segmental nerve than in the other (Table 3).…”