Acute optogenetic stimulation of serotonin neurons reduces cell proliferation in the dentate gyrus of mice

The dentate gyrus of the hippocampus is targeted by axons from serotonin raphe neurons, where the neurotransmitter modulates adult neurogenesis and antidepressant action, and mediates the neurogenic effect of running. Whether running-induced cell proliferation is directly mediated by serotonin remains unknown. Here, we took advantage of Tph2-ChR2-YFP transgenic mice in which the light-sensitive protein channelrhodopsin-2 (ChR2) is specifically expressed in tryptophan hydroxylase 2 (TPH2)-expressing neurons. We selectively activated serotonin neurons via optogenetics and determined the effect on cell proliferation in the dentate gyrus. Our data reveal a significant reduction in the number of newly generated cells upon overnight raphe stimulation. The decrease in cell proliferation was absent when serotonin neurons were light-activated for six consecutive nights. However, we observed an interhemispheric difference in BrdU-positive cell numbers. We conclude that acute network dynamics occur between serotonin raphe neurons and the hippocampus, directly affecting precursor cell proliferation.