It has been speculated that serotonin release in the forebrain is involved in model-based decision making. However, there is so far no direct evidence proving this hypothesis because there had been no method that selectively controls serotonergic activity. To resolve this problem, we developed transgenic mice expressing Archaerhodopsin T (ArchT) only in central serotonergic neurons. A lithium devaluation task was used to assess model-based decision making. In this paradigm, a mouse is first trained to poke its nose to illuminated holes to get a food pellet, and then the food is devalued by pairing it with lithium-induced illness. If the mouse associates the devaluation with nose-poking by mental simulation though the mouse has never experienced these two events simultaneously, the mice will refrain from poking its nose to holes (i.e. model based-decision making). Our results indicated that optogenetic silencing of serotonergic neurons in the dorsal raphe nucleus, but not the median raphe nucleus, impaired model-based decision making. Thus it is likely that serotonergic activity in the dorsal raphe nucleus has a pivotal role in model-based decision making.

To: 要旨(抄録)