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 [alpha]-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.

Glutamatergic reinnervation and assembly of glutamatergic synapses in adult rat skeletal muscle occurs at cholinergic endplates / M. Francolini, G. Brunelli, I. Cabianca, S. Barlati, A. Barbon, L. La Via, B. Guarnieri, F. Boroni, A. Lanzillotta, C. Baiguera, M. Ettorre, M. Buffelli, P.F. Spano, F. Clementi, M. Pizzi. - In: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. - ISSN 0022-3069. - 68:10(2009 Oct), pp. 1103-1115.

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

M. Francolini
;
F. Clementi
Penultimo
;
2009

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 [alpha]-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.
Acetylcholine receptors; AMPA receptors; Glutamate; Neuromuscular junction; Reinnervation; Spinal cord injury; Synaptic plasticity
Settore BIO/14 - Farmacologia
ott-2009
Article (author)
File in questo prodotto:
File Dimensione Formato  
1103.full.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 664.66 kB
Formato Adobe PDF
664.66 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/67865
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 15
social impact