Elucidation of neuronal circuit mechanisms of learning and memory for developing new drugs for cognitive impairments

Abstract

Memory retrieval is impaired due to the passage of a long time or neuronal degeneration. However, it is thought that the memory traces remain in the brain, as the forgotten memories are occasionally recollected spontaneously. Histamine neurons are located in the tuberomammillary nucleus, project to wide areas of the brain, and are involved in cognitive function, arousal, and food intake. Using multidisciplinary methods including mouse behavior analysis, manipulation and imaging of neuronal activity, and human clinical trials and demonstrated that activation of the brain histamine system restores retrieval of forgotten memories. Histamine promotes reactivation of perirhinal cortex neurons that are engaged in the initial learning. These findings contribute to development of new drugs treating cognitive impairments. In this presentation, I would like to introduce our recent findings and future directions using in vivo manipulation and imaging of neuronal activity.