Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Nature. 2011 Jan 20;469(7330):407-10. doi: 10.1038/nature09711. Epub 2010 Dec 19.
Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing. A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells. It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from a single genetically labelled type of DS cell. We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell.
神经连接的空间不对称性在构建神经元处理的基本构建块方面起着重要作用。方向选择性（DS）视网膜神经节细胞的一个关键电路模块是来自星状星形胶质细胞的空间不对称抑制性输入。目前尚不清楚这种电路不对称性在发育过程中是如何以及何时建立的。在这里，我们在用通道视紫红质-2（参考文献 6-8）靶向的小鼠星状细胞上进行光刺激，同时记录单个遗传标记的 DS 细胞。我们在这些神经元能够对生理光刺激做出反应之前，在早期出生后发育过程中跟踪星状细胞和 DS 细胞之间的突触强度的空间分布，并通过单突触限制的跨突触狂犬病毒追踪来确认连接。我们表明，通过已经建立的随机或对称突触连接的中间状态，对称性在两天内迅速发展。对称性的发展涉及抑制性突触输入的空间选择性重组织。有趣的是，在这个发育阶段结束时，星状细胞的兴奋性突触输入的空间分布明显比抑制性输入更对称。我们的工作证明了在主细胞的神经回路中，抑制作用从对称输入分布到不对称输入分布的快速发育转变。
