@phdthesis{oai:oist.repo.nii.ac.jp:00000816,
 author = {濱田, 太陽 and Hamada, Hiroaki},
 month = {2019-03-04, 2019-03-04},
 note = {Serotonin, one of the neuromodulators, is associated with multiple functions, such as the wake-sleep cycle, decision making, and mood. Serotonin is also the primary tar-get of medication for major depression (MD), notably by selective serotonin re-uptake inhibitors (SSRIs). However, it is widely known that serotonergic antidepressants re-quire long-term administration, and acute medication sometimes worsens symptoms.Serotonergic regulation of brain-wide dynamics remains crucial for understanding its roles in behavioral and cognitive functions as well as the mechanism of antidepressant medication.  First, I studied the influences of a serotonergic antidepressant on brain dynamics with functional magnetic resonance imaging in rodents. I found that the functional connectivity between the bed nucleus of steria terminalis (BST) and the ventral retrosplenial cortex (vRSC) distinctively responded to acute serotonergic antidepressant treatment, escitalopram. Additionally, long-term serotonergic antidepressant treatment promoted spontaneous locomotion and influenced anxiety like behaviors only in context-dependent and individually variable ways. The results imply that long-term serotonergic antidepressant treatment enhances intrinsic motivation,but not anxiety. Additionally, I analyzed large-scale brain dynamics with functional connectivity analysis and energy landscape analysis (ELA). My ELA analysis revealed that chronic administration of serotonergic antidepressants maintained dynamic brain states linking major attractor states, while conventional functional connectivity (FC)analysis did not show any difference caused by serotonergic antidepressants. The intermediate brain states, which are supported by modular integration, are associated with active exploration. My findings suggest that serotonergic antidepressants induce resilience by stabilizing brain state dynamics as a result of shaping functional network architecture. In the second study, I conducted a pilot experiment to assess serotonergic modulation of brain dynamics by optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN). In the first animal test, I found brain responses in the frontal cortical regions (the anterior cingulate cortex, the medial prefrontal cortex, and the insular cortex), the striatum, and the ventral tegmental area (VTA). In a reward delay task, optogenetic activation of DRN serotonin neurons enhanced waiting for delayed rewards, which confirmed the effectivenss of optogenetic stimulation. The result suggested the feasibility of studying serotonergic modulation with opto-fMRI. My thesis delineates how the serotonergic system regulates brain-wide dynamics at short- and long-term scales.},
 school = {Okinawa Institute of Science and Technology Graduate University},
 title = {セロトニンによる大規模脳活動制御},
 year = {}
}