Serotonin is a neurotransmitter closely related to various psychiatric disorders such as depression, anxiety, and drug addiction. Using serotonin neuron-selective viral vectors that we have developed, we would like to identify serotonergic neural circuits involved in emotional processing and decision-making processes. In particular, we are focusing our research on the opposite roles we have discovered: the serotonergic neurons of the dorsal raphe nucleus, which controls positive emotions, and the serotonergic neurons of the median raphe nucleus, which controls negative emotions. Through such analysis, we will realize the treatment of psychiatric disorders by selective modulation of serotonergic neuronal circuits.

Released serotonin regulates neuronal activity in both positive and negative directions via excitatory and inhibitory receptors, but it is unclear what happens in the brain as a result, causing behavioral changes such as antidepressant-like effects. We have found that serotonin selectively activates a group of cells involved in past pleasant memories in the hippocampus, the center of short-term memory, which is important for antidepressant-like effects. Through the discovery of these new functions of serotonin, we will elucidate the mechanisms that enable the brain to become more resilient to stress.

Degenerative loss of serotonergic neurons has been found in patients with Perry syndrome (Perry disease), an autosomal dominant genetic disease characterized by severe depressive symptoms. We are conducting research to elucidate the pathogenesis of the disease and to create a therapeutic drug using nucleic acid medicine, through differentiation of disease-specific iPS cells with a causative mutation into serotonergic neurons.