How we decide to do what we do is one of the most fundamental questions in understanding the neurobiological control of behavior. From moment to moment throughout our lives, we are constantly making cost/benefit analyses to generate action plans that optimize outcomes. In weighing up the costs of an outcome from an ethological standpoint, one must consider how much physical effort is required, how long a wait will there be before the outcome is presented, the certainty of the outcome and any possible aversive consequences. In addition, we have evolved to respect social and financial costs. Deficits in dealing with costs can be manifested as lethargy, impulsivity, risk taking or compulsion - traits that cross diagnostic categories of psychiatric disorders. Dopamine may play an important role in dealing with these costs. For example, antagonism of dopamine is sufficient to lower the physical effort rats will make, or the amount of time they will wait to obtain greater rewards. Subsecond activity in dopamine neurons encodes the outcome value within a range of available rewards, and these rapid signals can promote decisions to engage in behaviors to obtain rewards. We propose that this fast transmission provides a threshold signal for the costs an animal should endure to obtain a reward. Since they encode the expected reward amplitude, this would drive animals to tolerate a higher cost for better (expected) outcomes. In order to test this hypothesis, we will use a series of operant decision-making tasks that allow us to assess cost/benefit analysis and normalize across different costs, while measuring dopamine transmission with fast-scan cyclic voltammetry. In addition to investigating the subsecond temporal correlation between dopamine and behavior, we will also test causality of rapid dopamine release in cost/benefit decision making by electrically stimulating dopamine neurons. First, we will use a single-choice paradigm to test how dopamine in the nucleus accumbens encodes reward value and imposed effort or time costs. Next we will explore this signaling further when animals are choosing between two options that differ in reward magnitudes and in (time or effort) cost. Finally we will evoke dopamine release by electrically stimulating dopamine neurons at the exact time that an endogenous dopamine signal is generated - at the time of the initial stimulus at the start of the trial. This stimulation will boost the endogenous signal and thus test the effect of releasing more dopamine at the critical time during the behavior is sufficient to bias decision making towards higher-cost options. ? ? ?
Showing the most recent 10 out of 17 publications
