The role of midbrain dopamine neurons in reward prediction and reward seeking

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To succeed in their struggle for survival and reproductive success, animals must make wise choices about which goals to pursue and how much to pay and risk to attain them. How does the brain make such decisions and adjust behaviour accordingly? Neurobiologists, computer scientists, and psychologists have collaborated in developing an influential theory to answer these questions. The theory holds that dopamine cells in the brain adjust the accuracy of predictions about rewards and set the values assigned to reward-seeking actions. The activity of these dopamine neurons is posited to reflect the difference between the consequences that are expected and those that come to pass. This dopamine signal provides feedback to improve predictions of future outcomes and to choose the actions required to achieve them. One line of novel experiments will test the prediction-error theory in rats working for optical activation of dopamine cells. The release of dopamine will be monitored by miniature chemical sensors as the rats’ predictions and reward-seeking actions are measured. After encountering a valuable reward, such as a highly nutritious food item, it makes sense for a forager to immediately seek another. The more valuable the reward, the more vigorously the forager should do this. Such adaptively opportunistic behaviour has been documented in rats working for rewarding electrical brain stimulation. Dopamine neurons have been implicated strongly in reward seeking, yet the potentiation of reward seeking following exposure to a strong electrical reward was not reduced by a drug that blocks dopamine action in the brain. We will address this paradox by substituting direct, specific, optical activation of dopamine neurons for the indirect, non-specific activation produced by electrical stimulation. The results will help us understand the role of dopamine neurons in motivation. An animal’s assessment of potential benefits, detriments, costs, and risks must depend on its current physiological state. As internal energy stores empty, finding food becomes imperative, and the animal is willing to pursue expensive, risky courses of action to achieve this goal. We have long studied the dependence of reward seeking on energy balance in rats working for rewarding electrical brain stimulation. Recently, we applied a new method that distinguishes the effects of energy depletion on sensitivity to reward (which would make a food item seem more valuable) and on the animal’s assessment of the costs involved in procuring the reward (which would make a food item seem cheaper). I now propose to substitute optical stimulation of dopamine neurons for the electrical stimulation we have used previously, which is less specific and activates dopamine neurons indirectly. This work will help us better understand whether and how dopamine neurons link reward pursuit to the state of the internal physiological environment.