Nature—学习记忆机制研究重磅突破：成年人大脑的学习容量有多大，或许我们都错了！

中文摘要

哺乳动物皮层中新产生的兴奋性突触缺乏足够的AMPA型谷氨酸受体来介导神经传递，这些功能沉默的突触需要依赖活动的可塑性才能成熟。沉默的突触在早期发育中大量存在，在早期发育过程中，它们介导神经环路的形成和完善，但人们认为在成年人中沉默的突触很少。然而，事实上成年人仍具有神经可塑性和灵活学习的能力，这表明新连接的形成仍很普遍。在这里，科学家使用超高分辨率蛋白质成像来可视化成年小鼠初级视觉皮层第5层锥体神经元2234个突触的突触蛋白质。出乎意料的是，大约25%的突触缺乏AMPA受体。这些假定的沉默突触位于被称为丝足类的细树枝状突起的顶端，其数量比先前认为的要多一个数量级（占所有树枝状突起约30%）。生理学实验表明，丝足确实缺乏AMPA受体介导的传递，但它们表现出NMDA受体介导突触传递。科学家进一步表明，通过Hebbian可塑性，丝足上功能性沉默的突触可以被激活，在神经元的输入矩阵中参与形成新的活跃连接。这些结果挑战了功能连接在成人皮层中基本固定的模型，并证明了一种灵活控制突触连接的新机制，该机制扩展了成熟大脑的学习能力。

英文摘要

Newly generated excitatory synapses in the mammalian cortex lack sufficient AMPA-type glutamate receptors to mediate neurotransmission, resulting in functionally silent synapses that require activity-dependent plasticity to mature. Silent synapses are abundant in early development, during which they mediate circuit formation and refinement, but they are thought to be scarce in adulthood1. However, adults retain a capacity for neural plasticity and flexible learning that suggests that the formation of new connections is still prevalent. Here we used super-resolution protein imaging to visualize synaptic proteins at 2,234 synapses from layer 5 pyramidal neurons in the primary visual cortex of adult mice. Unexpectedly, about 25% of these synapses lack AMPA receptors. These putative silent synapses were located at the tips of thin dendritic protrusions, known as filopodia, which were more abundant by an order of magnitude than previously believed (comprising about 30% of all dendritic protrusions). Physiological experiments revealed that filopodia do indeed lack AMPA-receptor-mediated transmission, but they exhibit NMDA-receptor-mediated synaptic transmission. We further showed that functionally silent synapses on filopodia can be unsilenced through Hebbian plasticity, recruiting new active connections into a neuron's input matrix. These results challenge the model that functional connectivity is largely fixed in the adult cortex and demonstrate a new mechanism for flexible control of synaptic wiring that expands the learning capabilities of the mature brain.

参考文献：Filopodia are a structural substrate for silent synapses in adult neocortex. Nature. 2022 Nov 30. doi: 10.1038/s41586-022-05483-6. Online ahead of print.

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