Opto-fMRI analysis for exploring the neuronal connectivity of the hippocampal formation in rats

Abstract

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.