The symptoms and behavioral abnormalities of brain diseases are thought to be caused by the dysfunction of neural circuits formed by numerous neurons. Virtual reality (VR) is used for behavioral tasks under head fixation and has the advantage of precise control of experimental conditions. In this review, we first overview the application of VR in rodent neuroscience, introduce our research on two-photon calcium imaging of the hippocampus of autism spectrum disorder (ASD) model mice navigating a VR environment, and then discuss how hippocampal dysfunction can relate to ASD phenotypes. By combining a VR system with two-photon microscopy, we clarified the formation of hippocampal CA1 place cell maps in mice undergoing spatial learning in VR. As mice learned, the number of place cells increased, and the density of cells that responded to places with behaviorally relevant features such as rewards and landmarks increased more than cells active elsewhere. Furthermore, many stable place cells responded at landmark and reward locations. Shank2-deficient ASD model mice spent more time running and received more rewards. In their hippocampal maps, the proportion of cells active at landmarks did not increase, whereas the proportion of cells active at rewards excessively increased. Individuals with ASD are known to show unique tendencies in their perception and cognition of the world around them, but the detailed brain mechanisms remain unclear. It is thus possible that some ASD cases involve cognitive mapping abnormalities, such as the distortion of hippocampal information representation that our study revealed.