Disparity in Neurotransmitter Release Probability among Competing Inputs during Neuromuscular Synapse Elimination

Abstract

Competition among the several motor axons transiently innervating neonatal muscle fibers results in an increasing disparity in the quantal content and synaptic territory of each competitor, culminating in the permanent loss of all but one axon from neuromuscular junctions. We asked whether differences in the probability of neurotransmitter release also contribute to the increasing disparity in quantal content among competing inputs, and when in the process of competition changes in release probability become apparent. To address these questions, intracellular recordings were made from dually innervated neonatal mouse soleus muscle fibers, and quantal content and paired-pulse facilitation were evaluated for each input. At short interpulse intervals, paired-pulse facilitation was significantly higher for the weaker input with the smaller quantal content than the stronger input with the larger quantal content. Because neurotransmitter release probability across all release sites is inversely related to the extent of facilitation observed after paired-pulse stimulation, this result suggests that release probability is lower for weak compared with strong inputs innervating the same junction. A disparity in the probability of neurotransmitter release thus contributes to the disparity in quantal content that occurs during synaptic competition. Together, this work suggests that an input incapable of sustaining a high release probability may be at a competitive disadvantage for synaptic maintenance.

Developmental changes in spinal motoneuron dendrites in neonatal mice

“…At P3, mouse pups, like rats (Westerga and Gramsberger, 1990), exhibit minimal ability to crawl effectively on a smooth surface, while they can support their weight against gravity and walk with alternating hindlimb stepping by P10 -11 (Jiang et al, 1999). Furthermore, the polyneuronal innervation that characterizes neuromuscular organization in newborn mice is gradually lost and disappears by the end of the second week of life (Brown et al, 1967;Kopp et al, 2000). The relatively stable topology of lumbosacral MNs seems curiously at odds with this marked maturation of neuromuscular and functional organization.…”

Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination

“…Intracellular recording from soleus skeletal muscle fibers was performed by using glass microelectrodes filled with 3 M KCl (50-70 MÙ resistance) as described (28,43); see SI Methods.…”

“…The proportion of multiply and singly innervated neuromuscular junctions was determined by using intracellular recording from muscle fibers in an in vitro soleus nerve-muscle preparation in which the soleus nerve was split into two bundles and each placed into a different suction electrode (28). For each impaled muscle fiber, the nerve bundle in each suction electrode was stimulated at the lowest threshold for recording the end plate potential (epp).…”

Role for the skeletal muscle action potential in non‐Hebbian long‐term depression at the amphibian (Bufo marinus) neuromuscular junction

“…This can be seen during development and re-innervation of muscle when individual fibers receive transient innervation from two or more motoneurons (Wyatt and Balice-Gordon, 2003). Differences emerge in the strength of convergent inputs during the subsequent loss of the polyneuronal innervation of the muscle cell, and a role for activity-dependent retrograde modulation of synaptic strength in this process has been postulated (Colman et al, 1997;Kopp et al, 2000).…”

“…Lo and Poo (1991), for example, induced sustained depression of transmitter release from a neuron synapsing with a cultured myocyte by delivering a train of electrical stimuli to a different neuron coinnervating the same postsynaptic cell. It has been suggested that Hebbian depression at the immature neuromuscular junction, which leads to suppression of transmitter release from less active synaptic inputs, may contribute to the disparity in transmitter release from competing inputs that is observed during synaptic elimination (Colman et al, 1997;Kopp et al, 2000).…”