To elucidate neural circuit dysfunction behind behavioral abnormalities in brain disorders, it is essential to understand how external and internal information is represented in healthy and diseased brains by measuring the large-scale neural circuit activity of behaving animals with high resolution. Over years, we developed a procedure for in vivo deep brain imaging, transgenic mice expressing fluorescent calcium indicator proteins in the brain, and a virtual reality system for head-fixed mice to visualize the hippocampal neural circuit activity during virtual navigation by single-cell resolution two-photon calcium imaging. In basic neuroscience, virtual reality has long been used for behavioral tasks in human and primate brain research, and its importance has increased in recent years as an experimental paradigm for rodents as well. In my introductory talk, I will briefly outline the background of this methodology and present our recent study that investigated the formation and plasticity of hippocampal representation for reward and landmark in a mouse model of autism spectrum disorders.