In Vivo Imaging of the Coupling between Neuronal and CREB Activity in the Mouse Brain
In Vivo Imaging of the Coupling between Neuronal and CREB Activity in the Mouse Brain
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小鼠大脑中神经元和 CREB 活动之间耦合的体内成像
DOI：
10.1016/j.neuron.2019.11.028
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发表时间：
2020-03-04
期刊：
影响因子：
16.2
通讯作者：
Yasuda, Ryohei
中科院分区：
文献类型：
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作者：
Laviv, Tal;Scholl, Benjamin;Yasuda, Ryohei
感官体验通过调节对长期突触可塑性和记忆调节至关重要的活性依赖性转录程序，引起神经元回路的长期修改。然而，它一直不可能精确地确定神经元活动模式和转录因子活动之间的相互作用。在这里，我们提出了一种使用双光子荧光寿命成像（2pFLIM）和新型FRET生物传感器的技术，以单细胞分辨率对CREB（一种对突触可塑性重要的活性依赖性转录因子）的体内信号进行长期成像。红移CREB传感器和GCaMP的同时成像允许探索经验如何塑造清醒小鼠新皮层中CREB和神经元活动之间的相互作用。黑暗饲养增加了CREB活性的敏感性Ca2+升高和延长CREB激活的持续时间超过24小时的视觉皮层。这项技术将使研究人员能够解开大脑中依赖经验的可塑性的转录动力学。
Sensory experiences cause long-term modifications of neuronal circuits by modulating activity-dependent transcription programs that are vital for regulation of long-term synaptic plasticity and memory. However, it has not been possible to precisely determine the interaction between neuronal activity patterns and transcription factor activity. Here we present a technique using two-photon fluorescence lifetime imaging (2pFLIM) with new FRET biosensors to chronically image in vivo signaling of CREB, an activity-dependent transcription factor important for synaptic plasticity, at single-cell resolution. Simultaneous imaging of the red-shifted CREB sensor and GCaMP permitted exploration of how experience shapes the interplay between CREB and neuronal activity in the neocortex of awake mice. Dark rearing increased the sensitivity of CREB activity to Ca2+ elevations and prolonged the duration of CREB activation to more than 24 h in the visual cortex. This technique will allow researchers to unravel the transcriptional dynamics underlying experience-dependent plasticity in the brain.