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

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 -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 -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.