Muscarinic control of cytoskeleton in perisynaptic glia.
Similar to astrocytes at CNS synapses, perisynaptic Schwann cells (PSCs) surround nerve terminals at the neuromuscular junction (NMJ). These special teloglial cells are sensitive to neurotransmitters and upregulate glial fibrillary acidic protein (GFAP) when deprived of synaptic activity. We found that activation of muscarinic acetylcholine receptors (mAChRs) at PSCs, but not purinergic (ATP and adenosine) or peptidergic [substance P (SP) and calcitonin gene-related peptide (CGRP)] receptors, prevented this upregulation. When applied onto single PSCs, muscarine evoked Ca2+ responses that fatigued but prevented upregulation of this glial cytoskeletal protein. Application of ATP onto single PSCs evoked Ca2+ signals that showed little fatigue, and GFAP upregulation occurred. Thus, Ca2+ signals alone cannot prevent GFAP upregulation in the PSCs. After blockade of cholinergic receptors by gallamine, neuronal activity was not effective in maintaining low GFAP levels in the perisynaptic glia. Last, immunohistochemistry disclosed mAChRs on PSCs and nearby fibroblasts. Thus, acetylcholine secreted by the nerve terminal acts on the PSCs via mAChRs to regulate GFAP. Cytoskeletal changes may influence perisynaptic glial functions, including growth, remodeling, and modulation of the synapse.
Georgiou
J
J
Department of Physiology, Medical Research Council Group in Nerve Cells and Synapses, and Neuroscience Network, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Robitaille
R
R
Charlton
M P
MP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D011894:Rana pipiens; D011976:Receptors, Muscarinic / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D015854:Up-Regulation
D005904:Glial Fibrillary Acidic Protein; D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; D002118:Calcium