Department of Neuroscience, Physiology and Pharmacology, University College London, 21 University Street, London WC1E 6DE, UK.
Nature. 2013 Apr 4;496(7443):96-100. doi: 10.1038/nature12015.
Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured and excitatory neurons form subnetworks that process related sensory information. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience--a process that may be facilitated by early electrical coupling between neuronal subsets--and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.
感觉处理发生在新皮层微电路中，其中突触连接高度结构化，兴奋性神经元形成子网络，处理相关的感觉信息。然而，皮质微电路中功能组织连接形成的发育机制尚不清楚。在这里，我们使用体内双光子钙成像和体外多细胞记录，直接将兴奋性突触连接模式与不同出生后年龄的小鼠视觉皮层中相邻层 2/3 锥体神经元的视觉反应特性相关联。尽管在睁眼时神经反应已经对视觉刺激高度选择性，但对相似视觉特征做出反应的神经元尚未优先连接，这表明特征选择性的出现并不依赖于局部突触连接的精确排列。在睁眼后，局部连接进行了广泛的重新组织：更多的连接选择性地形成在具有相似视觉反应的神经元之间，而在对视觉无反应的神经元之间的连接被消除，但整体连接率没有变化。我们提出了一个基于活动依赖性可塑性机制的皮质微电路发育的顺序模型，其中神经元首先通过在感觉经验开始之前选择前馈输入来获得特征偏好——这个过程可能通过神经元亚群之间的早期电耦合来促进——然后输入模式通过重新分配递归突触连接来形成功能子网。
