Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Laboratory for Sensory Circuit Formation, Riken Center for Developmental Biology, Kobe 650-0047, Japan.
Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Laboratory for Sensory Circuit Formation, Riken Center for Developmental Biology, Kobe 650-0047, Japan; Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Dev Cell. 2023 Jul 24;58(14):1221-1236.e7. doi: 10.1016/j.devcel.2023.05.004. Epub 2023 Jun 7.
In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. We find that spontaneous activity generated within the olfactory bulb is essential. We show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. Our results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.
在发育中的大脑中，活动依赖性重塑促进了精确的神经元连接形成。已知突触竞争有助于突触消除，但仍不清楚在突触后细胞内不同的突触如何相互竞争。在这里，我们研究了在发育重塑过程中，小鼠嗅球中的一个僧帽细胞如何修剪除一条主要树突以外的所有树突。我们发现，嗅球内产生的自发性活动是必不可少的。我们表明，一条树突上的强烈谷氨酸能输入引发 RhoA 活性的分支特异性变化，以促进剩余树突的修剪：NMDAR 依赖性局部信号抑制 RhoA 以防止其被修剪；然而，随后的神经元去极化诱导 RhoA 的全神经元激活以修剪未受保护的树突。NMDAR-RhoA 信号对于小鼠桶状皮层中的突触竞争也是必不可少的。我们的结果表明了一个普遍的原则，即通过突触间的活动依赖性侧抑制来建立神经元的离散感受野。
