Muscarinic control of cytoskeleton in perisynaptic glia

Similar to astrocytes at CNS synapses, perisynaptic Schwann cells (PSCs) su rround nerve terminals at the neuromuscular junction (NMJ). These special t eloglial cells are sensitive to neurotransmitters and upregulate glial fibr illary acidic protein (GFAP) when deprived of synaptic activity. We found t hat activation of muscarinic acetylcholine receptors (mAChRs) at PSCs, but not purinergic (ATP and adenosine) or peptidergic [substance P (SP) and cal citonin gene-related peptide (CGRP)] receptors, prevented this upregulation . When applied onto single PSCs, muscarine evoked Ca2+ responses that fatig ued but prevented upregulation of this glial cytoskeletal protein. Applicat ion of ATP onto single PSCs evoked Ca2+ signals that showed little fatigue, and GFAP upregulation occurred. Thus, Ca2+ signals alone cannot prevent GF AP upregulation in the PSCs. After blockade of cholinergic receptors by gal lamine, neuronal activity was not effective in maintaining low GFAP levels in the perisynaptic glia. Last, immunohistochemistry disclosed mAChRs on PS Cs and nearby fibroblasts. Thus, acetylcholine secreted by the nerve termin al acts on the PSCs via mAChRs to regulate GFAP. Cytoskeletal changes may i nfluence perisynaptic glial functions, including growth, remodeling, and mo dulation of the synapse.