報酬/嫌悪情報処理における正中縫線核セロトニン神経の役割

抄録

A critical role of serotonergic neurons has been shown in reward and aversive information processing. Rewarding stimuli activate serotoninergic neurons in the dorsal raphe nucleus (DRN), while optogenetic stimulation of DRN serotoninergic neurons elicits reward-like effects. However, pharmacological enhancement of serotonin neurotransmission produces neither rewarding nor aversive effects. These findings suggest the existence of another serotonergic neuron that plays an opposite role to DRN in processing reward and aversion information. Previous reports have suggested that the median raphe nucleus (MRN) is involved in processing negative emotional stimuli. To clarify the role of MRN serotoninergic neurons in these processing, we recorded changes in serotonergic activity in mice in response to rewarding and aversive stimuli. We also used optogenetic manipulation to test whether these changes were sufficient to induce rewarding and aversive behaviors. The GCaMP fluorescence from MRN serotonergic neurons decreased in response to rewarding stimuli and increased after aversive stimuli. Optogenetic inhibition of MRN serotonergic neurons induced reward-related behavior, while optogenetic stimulation elicited aversion-related behavior. Moreover, we found that the projection pathway of MRN serotonergic neurons to the interpeduncular nucleus was important for these information processes. These results suggest that MRN serotonergic neurons play a key role in processing reward and aversive information and have an opposite function to the DRN.