Conditional deletion of TrkB alters adult hippocampal neurogenesis and anxiety-related behavior.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which has been reported to regulate neurogenesis in the dentate gyrus, but the molecular control over this process remains unclear. We demonstrated that by activating TrkB receptor tyrosine kinase, BDNF controls the size of the surviving pool of newborn neurons at the time of connectivity. The TrkB-dependent decision regarding survival in these newborn neurons takes place at approximately four to six weeks of age. Before newborn neurons start to die they exhibit a drastic reduction in dendritic complexity and spine density, which may reflect a failure of these cells to integrate appropriately. Both the failure to become integrated, and subsequent dying, leads to impaired neurogenesisdependent plasticity and increased anxiety-like behavior in mice lacking a functional TrkB receptor in newborn neurons. Thus, our data demonstrate the importance of BDNF/TrkB signaling for the survival and integration of newborn neurons in the adult hippocampus and suggest a critical function of these neurons in regulating the anxiety state of the animal.