title: Paralysis elicited by spinal cord injury evokes selective disassembly of neuromuscular synapses with and without terminal sprouting in ankle flexors of the adult rat.
abstract: Neuromuscular junctions (NMJs) innervated by motor neurons below spinal cord injury (SCI) have been reported to remain intact despite the interruption of supraspinal pathways and the resultant loss of activity. Here we report notably heterogeneous NMJ responses to SCI that include overt synapse disassembly. Complete transection of the thoracic spinal cord of adult rats evoked massive sprouting of nerve terminals in a subset of NMJs in ankle flexors, extensor digitorum longus, and tibialis anterior. Many of these synapses were extensively disassembled 2 weeks after spinal transection but by 2 months had reestablished synaptic organization despite continuous sprouting of their nerve terminals. In contrast, uniform and persistent loss of acetylcholine receptors (AChRs) was evident in another subset of NMJs in the same flexors, which apparently lacked terminal sprouting and largely maintained terminal arbors. Other synapses in the flexors, and almost all the synapses in the ankle extensors, medial gastrocnemius, and soleus, remained intact, with little pre- or postsynaptic alteration. Additional deafferentation of the transected animals did not alter the incidence or regional distribution of either type of the unstable synapses, whereas cycling exercise diminished their incidence. The muscle- and synapse-specific responses of NMJs therefore reflected differential sensitivity of the NMJs to inactivity rather than to differences in residual activity. These observations demonstrate the existence of multiple subpopulations of NMJs that differ distinctly in pre- and postsynaptic vulnerability to the loss of activity and highlight the anatomical instability of NMJs caudal to SCI, which may influence motor deficit and recovery after SCI.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Burns
authors.forename: Sabiha
authors.initials: S
authors.lastname: Jawaid
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshihara
authors.forename: Srishti
authors.initials: S
authors.lastname: Bhagat
authors.forename: Marion
authors.initials: M
authors.lastname: Murray
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.forename: Alan
authors.initials: A
authors.lastname: Tessler
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000842:Ankle / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D010243:Paralysis / Q000209:etiology* / Q000473:pathology* / Q000534:rehabilitation; D010805:Physical Conditioning, Animal / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications*; D013997:Time Factors
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D009418:S100 Proteins; C489618:Sv2a protein, rat