Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle

Giorgio Brunelli, PierFranco Spano, Sergio Barlati, Bruno Guarneri, Alessandro Barbon, Roberto Bresciani, Marina Pizzi

Research output: Contribution to journalArticlepeer-review

Abstract

Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connecting skeletal muscle to the lateral white matter of the spinal cord by grafting the distal stump of the transected motor nerve produced functional muscle reinnervation. The restored neuromuscular activity became resistant to common curare blockers but sensitive to the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Analysis of the regenerated nerve disclosed new glutamatergic axons and the disappearance of cholinergic fibers. Many axons belonged to the supraspinal neurons located in the red nucleus and the brainstem nuclei. Finally, the innervated muscle displayed high expression and clustering of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits glutamate receptors 1 and 2. Our data suggest that supraspinal neurons can target skeletal muscle, which retains the plasticity to generate functional glutamatergic NMJ.

Original languageEnglish
Pages (from-to)8752-8757
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number24
DOIs
Publication statusPublished - Jun 14 2005

Keywords

  • Glutamate
  • Neuromuscular junction
  • Red nucleus

ASJC Scopus subject areas

  • Genetics
  • General

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