Antibody-mediated impairment and homeostatic plasticity of autonomic ganglionic synaptic transmission.
Antibodies against ganglionic acetylcholine receptors (AChR) are implicated as the cause of autoimmune autonomic ganglionopathy (AAG). To characterize ganglionic neurotransmission in an animal model of AAG, evoked and spontaneous excitatory post-synaptic potentials (EPSP) were recorded from neurons in isolated mouse superior cervical ganglia (SCG). In vitro exposure of ganglia to IgG from AAG patients progressively inhibited synaptic transmission. After passive transfer of antibody to mice, evoked EPSP amplitude decreased, and some neurons showed no synaptic responses. EPSP amplitude recovered by day 7 despite persistence of ganglionic AChR antibody in the mouse serum. There was a more persistent (at least 14-day) reduction in miniature EPSP amplitude consistent with antibody-mediated reduction in post-synaptic AChR. Although the quantal size was reduced, a progressive increase in the frequency of spontaneous synaptic events occurred, suggesting a compensatory increase in presynaptic efficacy. The quantal size returned to baseline by 21 days while the frequency remained increased for at least four weeks. Ganglionic AChR antibodies cause an impairment of autonomic ganglionic synaptic transmission. Homeostatic plasticity in autonomic neurotransmission could help explain the spontaneous clinical recovery seen in some AAG patients and may also play an important role in regulating normal autonomic reflexes.
Wang
Zhengbei
Z
Department of Neurology, UT Southwestern Medical Center, Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9036, USA.
Low
Phillip A
PA
Vernino
Steven
S
D000328:Adult; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D005725:Ganglia, Autonomic / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D011978:Receptors, Nicotinic / Q000276:immunology*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D055815:Young Adult
D007074:Immunoglobulin G; D011978:Receptors, Nicotinic