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Central serotonin (5-HT) orchestrates myriad cognitive processes and lies at the core of many stress-related psychiatric illnesses. However, the basic relationship between its brain-wide axonal projections and functional dynamics is not known. Here we combine optogenetics and fMRI to produce a brain-wide 5-HT evoked functional map. We find that DRN photostimulation leads to an increase in the hemodynamic response in the DRN itself, while projection areas predominately exhibit a reduction of cerebral blood volume mirrored by suppression of cortical delta oscillations. We find that the regional distribution of post-synaptically expressed 5-HT receptors better correlates with DRN 5-HT functional connectivity than anatomical projections. Our work suggests that neuroarchitecture is not the primary determinant of function for the DRN 5-HT. With respect to two 5-HT elevating stimuli, we find that acute stress leads to circuit-wide blunting of the DRN output, while the SSRI fluoxetine noticeably enhances DRN functional connectivity. These data provide fundamental insight into the brain-wide functional dynamics of the 5-HT projection system.

Original publication




Journal article


Nat Commun

Publication Date





Animals, Brain Mapping, Cerebral Cortex, Cerebrovascular Circulation, Dorsal Raphe Nucleus, Evoked Potentials, Visual, Female, Fluoxetine, Immobilization, Magnetic Resonance Imaging, Male, Mice, Mice, Transgenic, Optogenetics, Photic Stimulation, Receptors, Serotonin, Serotonergic Neurons, Serotonin, Serotonin Uptake Inhibitors, Stress, Psychological