Kyoto University · Neuroscience
Professor Kazuki Nagayasu's research lab focuses on the neurobiological mechanisms underlying mood regulation, with a central emphasis on serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). The lab investigates how these neurons modulate reward and aversion circuits, particularly through projections to the ventral tegmental area (VTA), and explores their role in mediating the effects of antidepressants and memory-related behaviors. Using advanced optogenetic, chemogenetic, and ex vivo slice electrophysiology techniques, the lab examines synaptic and neurochemical adaptations in serotonergic systems in response to stress, antidepressants, and neuromodulators such as acetylcholine. A key focus is understanding the delayed therapeutic onset of antidepressants and the circuit-specific regulation of serotonin release.
Figures are computed from collected data and may differ slightly.
Our findings indicate that the activity of DRN 5-HT neurons projecting to the VTA is a key modulator of balance between reward and aversion.
These results suggest the ketamine-induced serotonin release in medial prefrontal cortex is mediated by cholinergic neurons projecting from pedunculopontine tegmental nucleus to dorsal raphe nucleus via α4β2 nAChRs.
Major depressive disorder (MDD) is among the most common mental illnesses. Serotonergic (5-HT) neurons are central to the pathophysiology and treatment of MDD. Repeatedly recalling positive episodes is effective for MDD. Stimulating 5-HT neurons of the dorsal raphe nucleus (DRN) or neuronal ensembles in the dorsal dentate gyrus (dDG) associated with positive memories reverses the stress-induced behavioral abnormalities. Despite this phenotypic similarity, their causal relationship is unclear. Th
These results suggest that sustained exposure to SSRIs induces the augmentation of exocytotic 5-HT release, which is caused, at least in part, by the activation of AMPA/kainate receptors in the raphe slice cultures.
Most clinically-used antidepressants acutely increase monoamine levels in synaptic clefts, while their therapeutic effects often require several weeks of administration. Slow neuroadaptive changes in serotonergic neurons are considered to underlie this delayed onset of beneficial actions. Recently, we reported that sustained exposure of rat organotypic raphe slice cultures containing abundant serotonergic neurons to selective serotonin (5-HT) reuptake inhibitors (citalopram, fluoxetine and parox
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