Control of intertemporal choice by dorsal raphe serotonergic neurons

Abstract

While animals tend to prefer immediate rewards to delayed ones [1], delayed gratification is often advantageous [2]. Appropriate choice about future rewards is critical for survival. The dorsal raphe serotonergic neurons have been long implicated in the control of temporal discounting of reward [3] [4], but it is not clear whether their activities in fact direct the decision making process. In this thesis, I designed a cued intertemporal choice task for mice that allows the combination of highly specific genetic manipulations with sophisticated behavioral interrogations. The task utilizes odors to communicate upcoming reward contingencies to the mouse subjects. I found that optogenetically augmenting or silencing the activities of dorsal raphe serotonergic neurons precisely at decision epochs resulted in an increase or a reduction in the choice for the delayed and larger reward, respectively. These manipulations do not alter the subjects' choice in trials involving immediate rewards, suggesting that serotonin might only be important for conditions in which difficult trade-offs are required. I also demonstrated that the nucleus accumbens, a major component of the mesolimbic reward pathway, is a possible downstream target of the aforementioned serotonin action. Taken together, these results show that serotonergic neurons regulate inter-temporal choice behavior bidirectionally, possibly through actions in nucleus accumbens.