Tien Nai-Wen, Soto Florentina, Kerschensteiner Daniel
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Neuron. 2017 May 3;94(3):656-665.e4. doi: 10.1016/j.neuron.2017.04.016. Epub 2017 Apr 27.
Convergent input from different presynaptic partners shapes the responses of postsynaptic neurons. Whether developing postsynaptic neurons establish connections with each presynaptic partner independently or balance inputs to attain specific responses is unclear. Retinal ganglion cells (RGCs) receive convergent input from bipolar cell types with different contrast responses and temporal tuning. Here, using optogenetic activation and pharmacogenetic silencing, we found that type 6 bipolar (B6) cells dominate excitatory input to ONα-RGCs. We generated mice in which B6 cells were selectively removed from developing circuits (B6-DTA). In B6-DTA mice, ONα-RGCs adjusted connectivity with other bipolar cells in a cell-type-specific manner. They recruited new partners, increased synapses with some existing partners, and maintained constant input from others. Patch-clamp recordings revealed that anatomical rewiring precisely preserved contrast and temporal frequency response functions of ONα-RGCs, indicating that homeostatic plasticity shapes cell-type-specific wiring in the developing retina to stabilize visual information sent to the brain.
来自不同突触前伙伴的汇聚输入塑造了突触后神经元的反应。发育中的突触后神经元是独立地与每个突触前伙伴建立连接,还是平衡输入以获得特定反应,目前尚不清楚。视网膜神经节细胞(RGCs)从具有不同对比度反应和时间调谐的双极细胞类型接收汇聚输入。在这里,我们使用光遗传学激活和药物遗传学沉默,发现6型双极(B6)细胞主导对ONα-RGCs的兴奋性输入。我们构建了在发育中的回路中选择性去除B6细胞的小鼠(B6-DTA)。在B6-DTA小鼠中,ONα-RGCs以细胞类型特异性方式调整与其他双极细胞的连接性。它们招募新的伙伴,增加与一些现有伙伴的突触,并维持来自其他伙伴的恒定输入。膜片钳记录显示,解剖学上的重新布线精确地保留了ONα-RGCs的对比度和时间频率反应功能,这表明稳态可塑性塑造了发育中视网膜中细胞类型特异性的布线,以稳定发送到大脑的视觉信息。