Role of nucleus accumbens in effort-based decision-making

描述（由申请人提供）：成瘾有时被描述为一种决策障碍。为了做出适当的决定，人和动物必须权衡各种选择的利弊。然而，成瘾者很难评估与吸毒有关的成本，并将花费不成比例的体力和精神努力来获得毒品。为了理解这是如何发生的，我们必须首先研究努力是如何在大脑中表现出来的，以及这种表现是如何促成寻找的决定的

DESCRIPTION (provided by applicant): Addiction is sometimes described as a disorder of decision-making. To make appropriate decisions, people and animals must weigh both the benefits and the costs of the available options. Addicts, however, have difficulty assessing the costs associated with drug use, and will expend a disproportionate degree of physical and mental effort to obtain drug. To understand how this happens, we must first investigate how effort is represented in the brain, and how this representation contributes to the decision to seek rewards. The nucleus accumbens (NAc) - and especially dopamine (DA) signaling in the NAc core - has long been implicated in the exertion of effort to obtain reward. However, it remains unknown how neural signals in the NAc might support the decision to exert effort. Although many individual NAc neurons respond to reward- predictive cues, it is unclear how these neurons encode the effort associated with cues and choices, especially in the moment when the animal decides whether to pursue an effortful option. Moreover, it is not known how DA input to the NAc contributes to effort-related signaling. To address these issues, rats will be trained to perform a task in which they decide between two options (levers) that are associated with different levels of effort (number of required lever presses) and/or different amounts of sucrose reward. While rats are making these decisions, we will record the firing activity of individual neurons in the NAc. We hypothesize that NAc neurons will encode both reward and effort levels in such a way that their activity may contribute to the weighing of options and/or the implementation of the resulting decision. Next, we will microinject DA receptor blockers into NAc core and observe the effect on rats' choices. We expect that these drugs will disrupt effort-based decision-making such that rats will become unwilling to exert more effort to obtain more reward. Finally, using an innovative technique, we will microinject DA receptor blockers into the NAc while simultaneously recording the neural activity of NAc neurons. We hypothesize that blocking DA receptors will disrupt the representation of effort information by NAc neurons. Taken together, these experiments will clarify the role of the NAc and its dopaminergic inputs in the circuits that underlie decision-making processes in the normal brain. This is a key step towards understanding how these circuits might go awry in the addicted brain, potentially opening a path towards developing or improving therapies for drug addiction.