Differential delay of reinnervating axons alters specificity in the rat serratus anterior muscle

Grow, Wade A.; Kendall-Wassmuth, Eydie; Ulibarri, Catherine; Laskowski, Michael B.

doi:10.1002/neu.480260408

Cited by 6 publications

(6 citation statements)

References 43 publications

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“…The strong influence of time on the outcome after nerve lesions indicates that a time window exists within which regenerating axons must access the distal nerve stump to effectively reach the distal target organs,50 and that the best final results in the nonhuman primate are obtained if reinnervation occurs within 100 days after the nerve lesion. Other experimental models have shown marked reduction in the success of reinnervation after delayed nerve repair,62–64 and conversely, increased specificity of reinnervation after rapid compared to delayed reinnervation 65. Our current results may also help to explain previous work that has shown an enhancement of axon regeneration when predegenerated nerve grafts are compared to fresh nerve grafts for nerve repair 66–68.…”

Section: Discussionsupporting

confidence: 66%

Factors that influence peripheral nerve regeneration: An electrophysiological study of the monkey median nerve

Krarup

Archibald

Madison

2001

Annals of Neurology

168

109

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Regeneration in the peripheral nervous system is often incomplete though it is uncertain which factors, such as the type and extent of the injury or the method or timing of repair, determine the degree of functional recovery. Serial electrophysiological techniques were used to follow recovery from median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen-based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound muscle action potentials in the abductor pollicis brevis muscle, (2) the number and size of motor units in reinnervated muscle, and (3) compound sensory action potentials from digital nerve. A statistical model was used to assess the influence of three variables (repair type, nerve gap distance, and time to earliest muscle reinnervation) on the final recovery of the outcome measures. Nerve gap distance and the repair type, individually and concertedly, strongly influenced the time to earliest muscle reinnervation, and only time to reinnervation was significant when all three variables were included as outcome predictors. Thus, nerve gap distance and repair type exert their influence through time to muscle reinnervation. These findings emphasize that factors that control early axonal outgrowth influence the final level of recovery attained years later. They also highlight that a time window exists within which axons must grow through the distal nerve stump in order for recovery after nerve lesions to be optimal. Future work should focus on interventions that may accelerate the growth of axons from the lesion site into the distal nerve stump.

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Section: Discussionsupporting

confidence: 66%

Factors that influence peripheral nerve regeneration: An electrophysiological study of the monkey median nerve

Krarup

Archibald

Madison

2001

Annals of Neurology

168

109

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“…Third, in some muscles, maps are formed or sharpened by a completely intramuscular process of synapse elimination after connections have formed (Brown and Booth, 1983a,b;Bennett and Lavidis, 1984a,b). Fourth, intramuscular maps are partially restored during reinnervation after nerve damage, although all regenerating axons have equal and simultaneous access to the muscle (Brown and Hardman, 1987;Hardman and Brown, 1987;Laskowski and Sanes, 1988;DeSantis et al, 1992;Grow et al, 1995;Laskowski et al, 1998a). Together, these results suggest that motor neurons and some intramuscular structures bear complementary cues that vary with rostrocaudal position and bias synapse formation in favor of positionally matched partners.…”

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confidence: 82%

Positionally Selective Growth of Embryonic Spinal Cord Neurites on Muscle Membranes

et al. 1999

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Motor neurons from distinct positions along the rostrocaudal axis generally innervate muscles or muscle fibers from corresponding axial levels. These topographic maps of connectivity are partially restored after denervation or transplantation under conditions in which factors of timing and proximity are eliminated. It is therefore likely that motor neurons and some intramuscular structures bear cues that bias synapse formation in favor of positionally matched partners. To localize these cues, we studied outgrowth of neurites from embryonic spinal cord explants on carpets of membranes isolated from perinatal rat muscles. Neurites from rostral (cervical) and caudal (lumbar) spinal cord slices exhibit distinct growth preferences. In many instances, rostrally derived neurites grew selectively on membranes from forelimb muscles or from a single thoracic muscle (the serratus anterior) when given a choice between these membranes and membranes from hindlimb muscles or laminin. Caudally derived neurites almost never exhibited such rostral preferences, but instead preferred membranes from hindlimb muscles or a single hindlimb muscle (the gluteus) to rostral muscles or laminin. Likewise, spinal neurites exhibited distinct position-related preferences for outgrowth on membranes of clonal myogenic cell lines derived from specific rostral and caudal muscles. Taken together these results suggest that the membranes of motor axons and myotubes bear complementary labels that vary with rostrocaudal position and regulate neuromuscular connectivity.

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“…An important question is whether this topographic map can be re-established after denervation. Previous work from our laboratory and those of others has shown that the spinal motor neuron pools of some muscles re-establish a topographic map after their innervation has been interrupted Hardman and Brown, 1987;Laskowski and Sanes, 1988;DeSantis et al, 1992;Grow et al, 1995; see also Sanes, 1982, 1985). What we do not know are the mechanisms that guide regenerating axons to their appropriate muscle targets or the processes by which axons are prevented from innervating positionally inappropriate targets.…”

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confidence: 79%

“…Why these caudally directed neurites bypass rostral end plates is not understood, but some explanations can be proposed. First, there is a 4:1 ratio of rostral (C 6 ) to caudal (C 7 ) root axons that innervate the SA muscle (Grow et al, 1995). Second, caudal axons may be physically constrained from innervating vacant rostral end plates or, once at an end plate site, may be incapable of forming functional synapses.…”

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confidence: 99%

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Synaptic Competition during the Reformation of a Neuromuscular Map

et al. 1998

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We have been studying the mechanisms whereby pools of motor neurons establish a rostrocaudal bias in the position of their synapses in some skeletal muscles. The serratus anterior (SA) muscle of the rat displays a rostrocaudal topographic map before birth, and the topography is re-established after denervation. In this report, we explore the potential role of synaptic competition between innervating axons as a means of generating topographic specificity. We followed the progress of the reformation of this map in neonatal animals under conditions that enhanced the likelihood of observing synaptic competition. This was accomplished by forcing caudal axons to regenerate ahead of rostral axons onto a surgically reduced SA muscle. In this way, caudal (C7) motor neurons had unopposed access to vacated synaptic sites on the remaining rostral half of the SA before the return of the rostral (C6) axons. Intracellular recording revealed that 2 d after the second denervation, most of the reinnervated end plates contained only axons from the C7 branch; the remaining reinnervated end plates received input from C6 only or were multiply innervated by C6 and C7 axons. After 6 d, the pattern was reversed, with most end plates innervated exclusively by C6. After 17 d, axons from C6 were the sole input to reinnervated end plates. During the transition from C7- to C6-dominated input, at end plates coinnervated by C6 and C7 axons, the average quantal content from C6 was the same as that from C7; after 7 d, the quantal content of C6 was greater than that of C7. We have thus developed an experimental situation in which the outcome of synaptic competition is predictable and can be influenced by the positional labels associated with axons from different levels in the spinal cord.

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Differential delay of reinnervating axons alters specificity in the rat serratus anterior muscle

Cited by 6 publications

References 43 publications

Factors that influence peripheral nerve regeneration: An electrophysiological study of the monkey median nerve

Factors that influence peripheral nerve regeneration: An electrophysiological study of the monkey median nerve

Positionally Selective Growth of Embryonic Spinal Cord Neurites on Muscle Membranes

Synaptic Competition during the Reformation of a Neuromuscular Map

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