Verhage M, Maia A S, Plomp J J, Brussaard A B, Heeroma J H, Vermeer H, Toonen R F, Hammer R E, van den Berg T K, Missler M, Geuze H J, Südhof T C
Molecular Neuroscience, Rudolf Magnus Institute, University of Utrecht Medical Centre, Utrecht, Netherlands.
Science. 2000 Feb 4;287(5454):864-9. doi: 10.1126/science.287.5454.864.
Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections.
大脑功能需要神经元之间精确协调的连接。这些连接的建立被认为需要从生长中的轴突分泌的信号，随后在选定的神经元之间形成突触。在小鼠中删除单一蛋白质Munc18-1会导致在整个发育过程中突触小泡的神经递质分泌完全丧失。然而，这并不妨碍正常的大脑组装，包括分层结构、纤维通路和形态学上定义的突触的形成。组装完成后，神经元会发生凋亡，导致广泛的神经退行性变。因此，突触连接并不依赖于神经递质分泌，但它的维持却依赖于此。神经递质分泌可能起到验证已建立的突触连接的作用。
