One of the characteristics of the central nervous system is its plasticity, with for example a remarkable capacity to store new information. It was for long time thought that there was very little plasticity in terms of exchanging cells and that we essentially were limited to the neurons we were born with. It is now well established that new neurons are added to certain regions of the adult brain in most mammals, although it has been very difficult to study in humans.The proposed project aims to unveil the cell lineage producing new neurons in the adult human brain and to assess the extent of neurogenesis and how it may change in for example aging and neurological and psychiatric diseases. We propose to take advantage of the rapid development of sequencing technology to assess the origin and lineage of new cells in the human brain by phylogenetic fate mapping. This will be combined with the analysis of the turnover of neurons in the adult human brain by a retrospective birth dating methodology which we recently have developed based on the integration of nuclear bomb test derived 14C. This is a cross-disciplinary project that bridges from basic cell and molecular biology, latest generation DNA sequencing technology via clinical medicine and mathematical modeling to nuclear physics.A possible role for alterations in adult neurogenesis in the etiology of both depression and schizophrenia has recently received much interest. However, the link between neurogenesis and psychiatric diseases is based on a series of indirect indications, mainly in experimental animals. It is pivotal to gain direct information on the relationship between neurogenesis and psychiatric and neurological diseases in humans.