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The Journal of Neuroscience, September 3, 2008, 28(36):8983-8992; doi:10.1523/JNEUROSCI.5226-07.2008

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Development/Plasticity/Repair
NMDA Receptor Blockade Maintains Correlated Motor Neuron Firing and Delays Synapse Competition at Developing Neuromuscular Junctions

Kirkwood E. Personius,¹ James L. Karnes,² and Sara D. Parker¹

¹Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York 14214, and ²Division of Rehabilitation Science, D'Youville College, Buffalo, New York 14201

Correspondence should be addressed to Dr. Kirkwood E. Personius, Department of Rehabilitation Science, Kimball Tower Room 515, 3435 Main Street, Buffalo, NY 14214-3079. Email: kep7{at}buffalo.edu

Mammalian neuromuscular synapses undergo an activity-dependent competitive transition from multiple to single innervation during postnatal life. The presence of temporally correlated motor neuron activity, which, in part, is controlled by gap junctional coupling within the spinal cord, appears to modulate synapse elimination. Postnatal injection of dizocilpine maleate (MK801), a specific NMDA antagonist, has been shown to maintain gap junctional coupling among motor neurons. Thus, we tested the hypothesis that MK801 would maintain correlated motor neuron activity and delay postnatal synapse elimination. Temporally correlated motor neuron activity, which is normally lost during the second postnatal week, was maintained and synaptic competition was delayed by several days in 2-week-old mice injected daily with MK801. MK801 appears to modulate motor neuron activity patterns through enhancing mRNA expression of multiple connexins within the spinal cord and delaying motor neuron growth. Our results suggest that MK801 injection preserves correlated neural activity via both synaptic mechanisms and maintenance of gap junctional coupling among neurons within the spinal cord, ultimately delaying synapse elimination.

Key words: motor neuron; gap junctions; activity; neuromuscular junction; competition; MK801

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Received Nov. 26, 2007; revised July 15, 2008; accepted July 19, 2008.

Correspondence should be addressed to Dr. Kirkwood E. Personius, Department of Rehabilitation Science, Kimball Tower Room 515, 3435 Main Street, Buffalo, NY 14214-3079. Email: kep7{at}buffalo.edu

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