Glutamatergic reinnervation and assembly of glutamatergic synapses in adult rat skeletal muscle occurs at cholinergic endplates

Maura Francolini, Giorgio Brunelli, Ilaria Cambianica, Sergio Barlati, Alessandro Barbon, Luca La Via, Bruno Guarneri, Flora Boroni, Annamaria Lanzillotta, Cristina Baiguera, Michele Ettorre, Mario Buffelli, Pierfranco Spano, Francesco Clementi, Marina Pizzi

Research output: Contribution to journalArticlepeer-review

Abstract

After denervation of adult rat abdominal muscles, the postsynaptic apparatus of neuromuscular junctions (NMJs) retains its original architecture and clustering of acetylcholine receptors (AChRs). When descending fibers of the spinal cord are surgically diverted to this muscle by a nerve grafting procedure, supraspinal glutamatergic neurons can innervate muscle fibers and restore motor function; the newly formed NMJs switch from a cholinergic to a glutamatergic-type synapse. We show here that regenerating nerve endings contact the fibers in an area occupied by cholinergic endplates. These NMJs are morphologically indistinguishable from those in controls, but they differ in the subunit composition of AChRs. Moreover, by immunofluorescence and immunoelectron microscopy, new NMJs express glutamatergic synapse markers. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 partially colocalizes with AChRs, and vesicular glutamate transporter 2 is localized in the presynaptic compartment. Immunoprecipitation analysis of membranes from reinnervated muscle showed that AMPA receptor subunits GluR1 and GluR2 coimmunoprecipitate with rapsyn, the AChR-anchoring protein at the NMJ. Taken together, these results indicate that cholinergic endplates can be targeted by new glutamatergic projections and that the clustering of AMPA receptors occurs there.

Original languageEnglish
Pages (from-to)1103-1115
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number10
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Acetylcholine receptors
  • AMPA receptors
  • Glutamate
  • Neuromuscular junction
  • Reinnervation
  • Spinal cord injury
  • Synaptic plasticity.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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