Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Neurosci Res. 2012 Dec;74(3-4):248-55. doi: 10.1016/j.neures.2012.08.007. Epub 2012 Sep 5.
In recent years, optical stimulation of neurons that bear a light-gated cation channel, "Optogenetics", has opened a new avenue for exploring neuronal connectivity of the nervous system. In this study, we applied a technique, "Opto-fMRI", which combined optogenetics with blood oxygenation level-dependent (BOLD) functional MRI (fMRI), for examining the neuronal connectivity of the hippocampal formation in rats. Although the hippocampal formation is very important for memory formation and retrieval, there is little information on its neuronal connectivity, especially on its longitudinal axis of connection. For this purpose, we utilized a transgenic rat strain, expressing the light-gated cation channel channelrhodopsin-2 (ChR2) under the regulation of the Thy1.2 promoter which permits the expression of the integrated gene in neurons. After optical stimulation targeting the dentate gyrus of the transgenic rat, we detected BOLD response of not only the dentate gyrus (DG) but also at the CA3 area. In addition, we detected the longitudinal-axis activation of the hippocampus after optical stimulation. Our study suggests that Opto-fMRI could be a tool for exploring the neuronal connectivity of the hippocampal formation, to understand the neural basis of memory formation and retrieval.
近年来，光刺激携带光门阳离子通道的神经元，即“光遗传学”，为探索神经系统的神经元连接开辟了新途径。在这项研究中，我们应用了一种技术，“光功能磁共振成像（Opto-fMRI）”，它将光遗传学与血氧水平依赖（BOLD）功能磁共振成像（fMRI）结合起来，用于检查大鼠海马结构的神经元连接。尽管海马结构对于记忆的形成和提取非常重要，但关于其神经元连接的信息很少，特别是关于其长轴连接的信息。为此，我们利用了一种转基因大鼠品系，该品系在 Thy1.2 启动子的调控下表达光门阳离子通道通道视紫红质-2（ChR2），允许整合基因在神经元中表达。在针对转基因大鼠齿状回进行光刺激后，我们不仅检测到了齿状回（DG）的 BOLD 反应，还检测到了 CA3 区的 BOLD 反应。此外，我们还检测到了光刺激后海马的长轴激活。我们的研究表明，Opto-fMRI 可能是探索海马结构神经元连接的一种工具，有助于理解记忆形成和提取的神经基础。
