Single neocortical neurons are driven by populations of excitatory inputs, which form the basis of neuronal selectivity to features of sensory input. Excitatory connections are thought to mature during development through activity-dependent Hebbian plasticity1, whereby similarity between presynaptic and postsynaptic activity selectively strengthens some synapses and weakens others2. Evidence in support of this process includes measurements of synaptic ultrastructure and in vitro and in vivo physiology and imaging studies3-8. These corroborating lines of evidence lead to the prediction that a small number of strong synaptic inputs drive neuronal selectivity, whereas weak synaptic inputs are less correlated with the somatic output and modulate activity overall6,7. Supporting evidence from cortical circuits, however, has been limited to measurements of neighbouring, connected cell pairs, raising the question of whether this prediction holds for a broad range of synapses converging onto cortical neurons. Here we measure the strengths of functionally characterized excitatory inputs contacting single pyramidal neurons in ferret primary visual cortex (V1) by combining in vivo two-photon synaptic imaging and post hoc electron microscopy. Using electron microscopy reconstruction of individual synapses as a metric of strength, we find no evidence that strong synapses have a predominant role in the selectivity of cortical neuron responses to visual stimuli. Instead, selectivity appears to arise from the total number of synapses activated by different stimuli. Moreover, spatial clustering of co-active inputs appears to be reserved for weaker synapses, enhancing the contribution of weak synapses to somatic responses. Our results challenge the role of Hebbian mechanisms in shaping neuronal selectivity in cortical circuits, and suggest that selectivity reflects the co-activation of large populations of presynaptic neurons with similar properties and a mixture of strengths.

中文翻译：

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皮质反应选择性源自突触数量的强度


单个新皮质神经元由兴奋性输入群体驱动，这构成了神经元对感觉输入特征的选择性基础。兴奋性连接被认为在发育过程中通过活动依赖性赫布可塑性成熟，突触前和突触后活动之间的相似性选择性地增强了一些突触并削弱了其他突触2。支持这一过程的证据包括突触超微结构的测量以及体外和体内生理学和成像研究3-8。这些确凿的证据导致了这样的预测：少数强突触输入驱动神经元选择性，而弱突触输入与体细胞输出和整体调节活动的相关性较低6,7。然而，来自皮层回路的支持证据仅限于对相邻、相连的细胞对的测量，这就提出了这样的问题：这一预测是否适用于汇聚到皮层神经元的广泛突触。在这里，我们通过结合体内双光子突触成像和事后电子显微镜来测量接触雪貂初级视觉皮层（V1）中单个锥体神经元的功能特征兴奋性输入的强度。使用单个突触的电子显微镜重建作为强度的度量，我们没有发现任何证据表明强突触在皮层神经元对视觉刺激的反应的选择性中起主导作用。相反，选择性似乎是由不同刺激激活的突触总数产生的。此外，共同活动输入的空间聚类似乎是为较弱的突触保留的，从而增强了弱突触对体细胞反应的贡献。 我们的结果挑战了赫布机制在塑造皮质回路中神经元选择性方面的作用，并表明选择性反映了具有相似特性和混合优势的大量突触前神经元的共同激活。