The rate of neurogenesis in the dentate gyrus of the adult hippocampus is highly labile. Much of this lability is due to the exquisite sensitivity of the progenitor cells to glucocorticoids. Glucocorticoids have two principal roles: absolute levels regulate the proliferation rate of the progenitor cells, and the presence of an intact diurnal corticoid rhythm is an essential requirement for the action of two further controlling factors: serotonin and nitric oxide (NO). The stimulating actions of both the SSRI fluoxetine and L-NAME requires the diurnal rhythm of corticosterone. Therefore is there a common factor regulating progenitor proliferation that is sensitive to both serotonin and NO? Is this factor also dependent on an intact diurnal rhythm, or is its action downstream of this regulatory point? BDNF is a plausible candidate as a common factor regulating proliferation in the dentate gyrus the interaction between SSRI, BDNF and NO are the major focus of intrest.
