Hippocampal neurogenesis and depression.

Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Using radiological and genetic methods, we show that disrupting neurogenesis blocks behavioural responses to antidepressants. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioural effects of two classes of antidepressants. Similarly, a genetic strategy that ablates adult progenitor cells resulted in a lack of effect of antidepressants. In addition, we have identified a form of long-term potentiation in the dentate gyrus that is dependent on the presence of young neurons and which is stimulated by antidepressants. These findings suggest that the behavioural effects of chronic antidepressants require hippocampal neurogenesis and are mediated by an increased synaptic plasticity in the dentate gyrus.