Synaptic Competition during the Reformation of a Neuromuscular Map

Abstract

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.

A morphological technique for exploring neuromuscular topography expressed in the mouse gluteus maximus muscle

“…Using electrophysiological methods our lab previously reported in another muscle, the rat serratus anterior, that there is a rostrocaudal distribution of axon terminals onto the surface of the muscle (Laskowski and High, 1989;Laskowski and Sanes, 1987;Laskowski et al, 1998;Potluri et al, 2002). We confirmed this topography within the mouse gluteus maximus muscle using the same method (Potluri et al, 2002).…”

Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury

“…In the later stage, endplate elimination takes place such that regenerating axons should be able to replace all the grafted cells. This can occur because they receive signals from the spinal cord and they are synaptically more active helping them to win the synaptical competition [81,82,83]. Based on these results, we believe that cell therapy should be considered a potential therapeutic strategy to prevent muscle atrophy after peripheral nerve injuries.…”

Morphometric analysis of neuromuscular topography in the serratus anterior muscle

“…15 The rat SA was chosen because of the extensive body of research that has accumulated on this muscle. 14,15,17 Moreover, the thinness of the muscle permitted us to examine a higher percentage of the fibers from both superficial and deep surfaces. The rat pups were anesthetized and perfused through the left ventricle with Ringer's solution containing: 144 mM NaCl, 4 mM KCl, 1 mM MgCl 2 , 1 mM KH 2 PO 4 , 4 mM Hepes buffer, 11 mM glucose, and 5 mM CaCl 2 , pH 7.3.…”