小柯机器人

美国麻省理工学院麦戈文大脑研究所Mark T. Harnett团队近期取得重要工作进展，他们研究发现丝状伪足是成人新皮层沉默突触的结构基底。相关论文2022年11月30日在线发表于《自然》杂志上。

据介绍，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，导致功能沉默的突触需要活性依赖的可塑性才能成熟。沉默突触在早期发育中大量存在，在这个过程中，它们介导回路的形成和完善，但在成年期它们被认为是稀缺的。然而，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。

研究人员使用超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状伪足的细长树突状突起顶端，其数量比先前认为的要多一个数量级（占所有树突状突起约30%）。生理学实验表明，丝状伪足确实缺乏AMPA受体介导的传递，但它们表现出NMDA受体介导突触传递。

研究人员进一步表明，丝状伪足上功能沉默的突触可以通过Hebbian可塑性解除沉默，将新的活性连接招募到神经元的输入矩阵中。这些结果挑战了功能连接在成人皮层中基本固定的模型，并展示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。

附：英文原文

Title: Filopodia are a structural substrate for silent synapses in adult neocortex

Author: Vardalaki, Dimitra, Chung, Kwanghun, Harnett, Mark T.

Issue&Volume: 2022-11-30

Abstract: 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.

DOI: 10.1038/s41586-022-05483-6

Source: https://www.nature.com/articles/s41586-022-05483-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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