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The Journal of Neuroscience, June 20, 2007, 27(25):6712-6722; doi:10.1523/JNEUROSCI.1329-07.2007

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Cellular/Molecular
Schwann Cell-Derived Factors Modulate Synaptic Activities at Developing Neuromuscular Synapses

Guan Cao  and Chien-Ping Ko

Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-2520

Correspondence should be addressed to Dr. Chien-Ping Ko, Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2520. Email: cko{at}usc.edu

Glial cells are active participants in the function, formation, and maintenance of the chemical synapse. To investigate the molecular basis of neuron–glia interactions at the peripheral synapse, we examined whether and how Schwann cell-derived factors modulate synaptic function at developing neuromuscular junctions (NMJs). Schwann cell-conditioned medium (SC-CM) from Xenopus Schwann cell cultures was collected and applied to Xenopus nerve–muscle cocultures. We found that SC-CM increased the frequency of spontaneous synaptic currents (SSCs) within 3–15 min by an average of 150-fold at developing neuromuscular synapses. The increase in SSC frequency by SC-CM is a presynaptic effect independent of neuronal excitability and requires the influx of Ca²⁺. In contrast to its potentiating effect on spontaneous transmitter release, SC-CM suppressed the evoked transmitter release. The SC-CM effect required the presence of motoneuron soma but not protein synthesis. Using molecular weight cutoff filters and dialysis membranes, we found that the molecular weight of functional factor(s) in SC-CM was within 500 and 5000 Da. The SC-CM effect was not attributable to currently known factors that modulate synaptic efficacy, including neurotrophins, glutamate, and ATP. SC-CM also enhanced spontaneous synaptic release at developing NMJs in Xenopus tadpoles in situ. Our results suggest that Schwann cells release small molecules that enhance spontaneous synaptic activities acutely and potently at developing neuromuscular synapses, and the glial cell-enhanced spontaneous neurotransmission may contribute to synaptogenesis.

Key words: glia; neuromuscular junctions; neuron–glia interactions; Schwann cell; synaptic transmission; synaptogenesis

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Received March 25, 2007; revised May 7, 2007; accepted May 13, 2007.

Correspondence should be addressed to Dr. Chien-Ping Ko, Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2520. Email: cko{at}usc.edu

This article has been cited by other articles:

				Z. FENG and C.-P. KO The Role of Glial Cells in the Formation and Maintenance of the Neuromuscular Junction Ann. N.Y. Acad. Sci., June 1, 2008; 1132(1): 19 - 28. [Abstract] [Full Text] [PDF]

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