The precise control of neural activities at both cellular and circuit levels reveals significant impacts on the fundamental neuroscience explorations and medical applications. Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable and being actively researched. Here we report bidirectional neuronal activity manipulation accomplished by a wireless, dual-color optogenetic probe in synergy with the co-expression of two spectrally distinct opsins (ChrimsonR and stGtACR2) in a rodent model. Based on vertically assembled, thin-film microscale light-emitting diodes (micro-LEDs) with a lateral dimension of 125 × 180 µm² on flexible substrates, the dual-color probe shows colocalized red and blue emissions and allows chronic in vivo operations with desirable biocompatibilities. In addition, we discover that neurons co-expressing the two opsins can be deterministically evoked or silenced under red or blue irradiations. Implanted in behaving mice, the wirelessly controlled dual-color probe interferes with dopaminergic neurons in the ventral tegmental area (VTA), increasing or decreasing dopamine levels with colocalized red and blue stimulations. Such bidirectional regulations further generate rewarding and aversive behaviors of freely moving mice in a place preference test and interrogate social interactions among multiple mice. The technologies established here will create numerous opportunities and profound implications for brain research.

中文翻译：

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使用无线双色光电探针对自由行为小鼠进行共定位双向光遗传学调制

在细胞和电路水平上对神经活动的精确控制揭示了对基础神经科学探索和医学应用的重大影响。光遗传学方法提供了有效的细胞特异性调节，并且在自由活动动物的同一大脑区域中同时进行神经激活和抑制的能力是非常可取的，并且正在积极研究中。在这里，我们报告了通过无线双色光遗传学探针与啮齿动物模型中两种光谱不同的视蛋白（ChrimsonR 和 stGtACR2）的共表达协同完成的双向神经元活动操作。基于垂直组装的薄膜微型发光二极管 (micro-LED)，横向尺寸为 125 × 180 µm ²在柔性基板上，双色探针显示出共定位的红色和蓝色发射，并允许在体内慢性具有理想的生物相容性的操作。此外，我们发现共同表达两种视蛋白的神经元可以在红色或蓝色照射下确定性地诱发或沉默。植入行为小鼠体内，无线控制的双色探针干扰腹侧被盖区 (VTA) 的多巴胺能神经元，通过共定位的红色和蓝色刺激增加或降低多巴胺水平。这种双向调节进一步产生了在位置偏好测试中自由移动的老鼠的奖励和厌恶行为，并询问多只老鼠之间的社交互动。这里建立的技术将为大脑研究创造大量机会和深远的影响。