Effect of partial denervation and terminal field expansion on neuromuscular transmitter release and nerve terminal structure

Abstract

The efficacy of evoked ACh release by intact and newly sprouted terminals in response to partial denervation and expansion of the motor neuron terminal field was studied in mouse soleus muscle after section of the L-5 spinal root. From 2 to 4 d after partial denervation until 90 d later, only 3-7 motor units of the normal 21 remained. Regeneration of the dissected nerve was prevented while the remaining motor units were sprouting. The indirect twitch, which was only 20% of direct twitch tension 2-4 d after nerve section, recovered between 28 and 50 d postoperatively. However, the depression of twitch in low Ca/high Mg solution, which was equal to control 2-3 d postoperatively, was 2-3 times more depressed than control by 50 d and remained so up to 90 d. This indicated persistent reduction of the safety factor in sprouted motor units. Intracellular measurement of quantal content in 0.4 mM Ca, 2.75 mM Mg revealed 2 groups of nerve terminals in partially denervated muscle. The quantal content of the first group was greater than contralateral control at earlier times (28-50 d) and only slightly greater than control later (74 and 90 d). This group consisted of the original undenervated terminals, since it was associated with normal miniature endplate potential (MEPP) frequency and end-plate potential (EPP) latency, and presumably with the class of fibers with normal (zinc iodide osmium-stained) nerve terminal morphology and occasional large myelinated preterminal axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

“…For example, the perikaryon of ES-cellderived MNs may have a reduced capacity to supply synaptic components to an expanded number of NMJs. Indeed, an effective safety factor of neurotransmission at the NMJ is an important factor limiting MU size in partially denervated muscles (Rochel and Robbins, 1988). Alternatively, ES-cell-derived MNs may contain fewer proximal branches.…”

Presynaptic NCAM Is Required for Motor Neurons to Functionally Expand Their Peripheral Field of Innervation in Partially Denervated Muscles

“…These changes range from local adjustments in synaptic strength (Branco et al, 2008;Béïque et al, 2011) to widespread reorganization of axonal terminal fields (Brown and Ironton, 1978;Rochel and Robbins, 1988;Schaefer et al, 2005). An example of large-scale synaptic reorganization occurs in skeletal muscles partially denervated by injury (Brown and Ironton, 1978;Rochel and Robbins, 1988;Rafuse et al, 1992).…”

“…These changes range from local adjustments in synaptic strength (Branco et al, 2008;Béïque et al, 2011) to widespread reorganization of axonal terminal fields (Brown and Ironton, 1978;Rochel and Robbins, 1988;Schaefer et al, 2005). An example of large-scale synaptic reorganization occurs in skeletal muscles partially denervated by injury (Brown and Ironton, 1978;Rochel and Robbins, 1988;Rafuse et al, 1992). Favorable outcomes of partially denervated muscles require directed growth of axonal sprouts along Schwann cell bridges that extend from innervated end plates to denervated synapses (Son and Thompson, 1995), the accumulation of synaptic resources at newly formed terminals, and the stabilization of neurotransmission at reinnervated sites (Rochel and Robbins, 1988;Schaefer et al, 2005).…”

“…An example of large-scale synaptic reorganization occurs in skeletal muscles partially denervated by injury (Brown and Ironton, 1978;Rochel and Robbins, 1988;Rafuse et al, 1992). Favorable outcomes of partially denervated muscles require directed growth of axonal sprouts along Schwann cell bridges that extend from innervated end plates to denervated synapses (Son and Thompson, 1995), the accumulation of synaptic resources at newly formed terminals, and the stabilization of neurotransmission at reinnervated sites (Rochel and Robbins, 1988;Schaefer et al, 2005). Failure to establish any one of these processes hinders functional recovery, and their malfunction may underlie some of the pathophysiology associated with motor neuron diseases such as amyotrophic lateral sclerosis (ALS; Gordon et al, 2004;Fischer and Glass, 2007).…”

“…The sprouting capacity of a single motor neuron is determined by its growth potential and its ability to maintain effective neurotransmission across supernumerary synapses (Rochel and Robbins, 1988;Rafuse et al, 1992). Healthy motor neurons in partially denervated muscles can sprout and expand their field of innervation to form motor units (MUs) four to five times their original size (Rafuse et al, 1992).…”