Final Report Summary - AN07AT (Understanding computational roles of new neurons generated in the adult hippocampus)
New neurons are continuously generated in certain regions of adult mammalian brain. One of those regions is the dentate gyrus, a subregion of hippocampus, which is essential for memory formation. Although these new neurons in the adult dentate gyrus are thought to have an important role in learning and memory, it is largely unclear how new neurons are involved in information processing and storage underlying memory. Because new neurons constitute a minor portion of intermingled local neuronal population, simple application of conventional techniques such as multi-unit extracellular recording and pharmacological lesion are not suitable for the functional analysis of new neurons. In this project, we have combine multi-unit recording and behavioral analysis with virus mediated, cell-type-specific genetic manipulation of neuronal activity, to investigate computational roles of new neurons in learning and memory and how neuronal activity in the dentate gyrus affects neurogenesis.. Specifically, 1) we showed that young, newly-generated neurons play a role in memory process after initial memory acquisition. 2) neuronal activity in the dentate gyrus may define neurogenic environment in the dentate gyrus. 3) we developed an optogenetic marking method to record from identified granule cells, which would form a methodological basis of further extention to recording identified newborn neurons. Thus, using the state of the art methodology, we advanced our understanding of how newly-generated neurons contribute to memory process, and how memory process mediated by neuronal activity influence neurogenesis in the dentate gyrus. The information on the function and mechanism of adult neurogenesis in normal brain could contribute to future development of efficient therapeutic strategy for a variety of brain disorders.