کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4342491 1295871 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
α-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
α-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction
چکیده انگلیسی

Neurotransmission at chemical synapses of the brain involves α-neurexins, neuron-specific cell-surface molecules that are encoded by three genes in mammals. Deletion of α-neurexins in mice previously demonstrated an essential function, leading to early postnatal death of many double-knockout mice and all triple mutants. Neurotransmitter release at central synapses of newborn knockouts was severely reduced, a function of α-neurexins that requires their extracellular sequences. Here, we investigated the role of α-neurexins at neuromuscular junctions, presynaptic terminals that lack a neuronal postsynaptic partner, addressing an important question because the function of neurexins was hypothesized to involve cell-adhesion complexes between neurons. Using systems physiology, morphological analyses and electrophysiological recordings, we show that quantal content, i.e. the number of acetylcholine quanta released per nerve impulse from motor nerve terminals, and frequency of spontaneous miniature endplate potentials at the slow-twitch soleus muscle are reduced in adult α-neurexin double-knockouts, consistent with earlier data on central synapses. However, the same parameters at diaphragm muscle neuromuscular junctions showed no difference in basal neurotransmission. To reconcile these observations, we tested the capability of control and α-neurexin-deficient diaphragm neuromuscular junctions to compensate for an experimental reduction of postsynaptic acetylcholine receptors by a compensatory increase of presynaptic release: Knockout neuromuscular junctions produced significantly less upregulation of quantal content than synapses from control mice. Our data suggest that α-neurexins are required for efficient neurotransmitter release at neuromuscular junctions, and that they may perform a role in the molecular mechanism of synaptic homeostasis at these peripheral synapses.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 138, Issue 2, 2006, Pages 433–446
نویسندگان
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