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Acute optogenetic stimulation of serotonergic neurons in raphe nuclei reduces cell proliferation in the dentate gyrus of the mouse ; Akute optogenetische Stimulation von serotonergen Neuronen in Raphe-Kernen reduziert Zellproliferation im Gyrus dentatus der Maus
The subgranular zone of the hippocampal dentate gyrus (DG) is known to be replenished with new-born neurons even after fetal and early postnatal development has completed, a phenomenon called adult neurogenesis. Functions of these new-born neurons and regulatory mechanisms of adult neurogenesis are not fully understood. The DG receives various synaptic inputs including those from serotonergic neurons in the brain stem raphe nuclei. Previous studies in mice have suggested that physical activities enhance neurogenesis via serotonergic neurotransmission. In the present study, the influence of serotonin (5-HT) on adult neurogenesis was investigated by directly activating serotonergic neurons in the dorsal and median raphe nucleus (DRN, MRN) using optogenetics. Specifically, cell proliferation was examined by bromodeoxyuridine (BrdU) labeling in the DG after overnight and one-week optogenetic activation of serotonergic neurons in the raphe nuclei in freely behaving tryptophan hydroxylase 2-channelrhodopsin 2 (Tph2-ChR2) transgenic mice. These mice express photo-excitable cation channels, ChR2, under the control of the Tph2 promoter, allowing specific activation of serotonergic neurons. First, specific activation of serotonergic neurons in the DRN or MRN was electrophysiologically confirmed in brain slices and in anesthetized mice. In consequence of the optogenetic activation of serotonergic neurons in the DRN or MRN, a reduction in firing rates was observed in the DG in the anesthetized mice. After overnight stimulation of serotonergic neurons in the freely behaving animals, BrdU-positive cells in the DG were significantly reduced in number compared to non-stimulated control mice. The total distances traveled did not differ significantly between stimulated and non-stimulated mice, indicating that the reduced cell proliferation in the DG was not due to reduced physical movement. Further, as revealed by high-performance liquid chromatography (HPLC), reduced cell proliferation in the DG was accompanied by reduced 5-HT ...
Acute optogenetic stimulation of serotonergic neurons in raphe nuclei reduces cell proliferation in the dentate gyrus of the mouse ; Akute optogenetische Stimulation von serotonergen Neuronen in Raphe-Kernen reduziert Zellproliferation im Gyrus dentatus der Maus
The subgranular zone of the hippocampal dentate gyrus (DG) is known to be replenished with new-born neurons even after fetal and early postnatal development has completed, a phenomenon called adult neurogenesis. Functions of these new-born neurons and regulatory mechanisms of adult neurogenesis are not fully understood. The DG receives various synaptic inputs including those from serotonergic neurons in the brain stem raphe nuclei. Previous studies in mice have suggested that physical activities enhance neurogenesis via serotonergic neurotransmission. In the present study, the influence of serotonin (5-HT) on adult neurogenesis was investigated by directly activating serotonergic neurons in the dorsal and median raphe nucleus (DRN, MRN) using optogenetics. Specifically, cell proliferation was examined by bromodeoxyuridine (BrdU) labeling in the DG after overnight and one-week optogenetic activation of serotonergic neurons in the raphe nuclei in freely behaving tryptophan hydroxylase 2-channelrhodopsin 2 (Tph2-ChR2) transgenic mice. These mice express photo-excitable cation channels, ChR2, under the control of the Tph2 promoter, allowing specific activation of serotonergic neurons. First, specific activation of serotonergic neurons in the DRN or MRN was electrophysiologically confirmed in brain slices and in anesthetized mice. In consequence of the optogenetic activation of serotonergic neurons in the DRN or MRN, a reduction in firing rates was observed in the DG in the anesthetized mice. After overnight stimulation of serotonergic neurons in the freely behaving animals, BrdU-positive cells in the DG were significantly reduced in number compared to non-stimulated control mice. The total distances traveled did not differ significantly between stimulated and non-stimulated mice, indicating that the reduced cell proliferation in the DG was not due to reduced physical movement. Further, as revealed by high-performance liquid chromatography (HPLC), reduced cell proliferation in the DG was accompanied by reduced 5-HT ...
Acute optogenetic stimulation of serotonergic neurons in raphe nuclei reduces cell proliferation in the dentate gyrus of the mouse ; Akute optogenetische Stimulation von serotonergen Neuronen in Raphe-Kernen reduziert Zellproliferation im Gyrus dentatus der Maus
Araragi, Naozumi (author) / male / N.N.
2024-01-01
Theses
Electronic Resource
English
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