Alterations in Synaptic Strength Preceding Axon Withdrawal

Abstract

Permanent removal of axonal input to postsynaptic cells helps shape the pattern of neuronal connections in response to experience, but the process is poorly understood. Intracellular recording from newborn and adult mouse muscle fibers temporarily innervated by two axons showed an increasing disparity in the synaptic strengths of the two inputs before one was eliminated. The connection that survived gained strength by increasing the amount of neurotransmitter released (quantal content), whereas the input that was subsequently removed became progressively weaker, because of a reduction in quantal content and a reduction in quantal efficacy associated with reduced postsynaptic receptor density. Once the synaptic strengths of two inputs began to diverge, complete axonal withdrawal of the weaker input occurred within 1 to 2 days. These experiments provide a link between experience-driven changes in synaptic strength and long-term changes in connectivity in the mammalian nervous system.

Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

“…At later stages of synapse maturation, however, one cell wins the full compliment of synaptic strength, whereas the other synapse is eliminated. This is reminiscent of synapse elimination at the neuromuscular junction, whereby supernumerary innervation persists as long as the inputs from all presynaptic neurons are of equal strength (Colman et al, 1997;Sanes and Lichtman, 1999). As soon as the balance is tipped in favor of one of the neurons, the weaker synapse is eliminated and the stronger prevails (Colman et al, 1997).…”

“…Both activity-dependent (Nguyen and Lichtman, 1996;Colman et al, 1997;Sanes and Lichtman, 1999;Ichise et al, 2000;Stellwagen and Shatz, 2002) and -independent (Nguyen and Lichtman, 1996;Nguyen et al, 1998) mechanisms have been proposed to account for the elimination of exuberant synapses. One attractive model is that active synapses receive trophic support at the expense of inactive synapses, which are consequently retracted (Nguyen et al, 1998;Sanes and Lichtman, 1999).…”

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).…”

Steps to a neurochemistry of personality

“…Experience-dependent processes encode experience unique to the individual through interactions of neurotransmitter systems that modulate dendritic outgrowth, synaptogenesis, and synaptic regression Colman et al 1997;Magee & Johnston 1997;Mattson 1988). Through these mechanisms, neurotransmitter activity may regulate synaptic connectivity within the distributed structures of a particular neural network (Uno & Ozawa 1991).…”