Miyasaka Yumi, Yamamoto Nobuhiko
Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Front Neurosci. 2021 Dec 10;15:699583. doi: 10.3389/fnins.2021.699583. eCollection 2021.
During development, cortical circuits are remodeled by spontaneous and sensory-evoked activity alteration of the expression of wiring molecules. An intriguing question is how physiological neuronal activity modifies the expression of these molecules in developing cortical networks. Here, we addressed this issue, focusing on brain-derived neurotrophic factor (BDNF), one of the factors underlying cortical wiring. Real-time imaging of BDNF promoter activity in organotypic slice cultures revealed that patterned stimuli differentially regulated the increase and the time course of the promoter activity in upper layer neurons. Calcium imaging further demonstrated that stimulus-dependent increases in the promoter activity were roughly proportional to the increase in intracellular Ca concentration per unit time. Finally, optogenetic stimulation showed that the promoter activity was increased efficiently by patterned stimulation in defined cortical circuits. These results suggest that physiological stimulation patterns differentially tune activity-dependent gene expression in developing cortical neurons cortical circuits, synaptic responses, and alteration of intracellular calcium signaling.
在发育过程中，皮质回路通过自发活动和感觉诱发活动对布线分子表达的改变而进行重塑。一个有趣的问题是，生理神经元活动如何在发育中的皮质网络中改变这些分子的表达。在这里，我们聚焦于脑源性神经营养因子（BDNF），它是皮质布线的基础因子之一，来解决这个问题。器官型脑片培养中BDNF启动子活性的实时成像显示，模式化刺激差异性地调节上层神经元中启动子活性的增加和时间进程。钙成像进一步表明，启动子活性的刺激依赖性增加大致与单位时间内细胞内钙浓度的增加成正比。最后，光遗传学刺激表明，在特定的皮质回路中，模式化刺激能有效增加启动子活性。这些结果表明，生理刺激模式差异性地调节发育中皮质神经元的活动依赖性基因表达，进而影响皮质回路、突触反应以及细胞内钙信号的改变。
