Evaluation of costs and benefits of actions in the basal ganglia

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We propose to investigate how the brain evaluates the costs and benefits of available options during decision making. We focus on a part of the brain called the basal ganglia that plays an important role in action selection, or a decision about which movement to take. This part of the brain is also involved in the evaluation of options during more abstract decisions. In the basal ganglia there are two main groups of neurons: One group has been shown to facilitate the choice or movement, and we refer to them as the Go neurons, while the other group has been shown to block or prevent movements, and we refer to them as the No-Go neurons. The activity of these two types of neurons is modulated by another population of neurons which release a chemical substance called dopamine. The presence of dopamine increases the activity of Go neurons and decreases the activity of No-Go neurons.Despite years of studies, it is still highly debated what the functions of these two groups of neurons are. One dominant hypothesis is that the while Go neurons facilitate an action, the No-Go neurons block alternative choices, to ensure that only one action is chosen at the time. Alternatively, it has been recently proposed that the Go and No-Go neurons encode the payoffs and costs of actions, while the dopaminergic neurons encode the current motivational state, e.g. hunger. This theory suggests that the basal ganglia circuit weights the payoffs and costs differently according to the motivational state. For example, when an animal is hungry, a high level of dopamine increases the activity of Go neurons and decreases the activity of No-Go neurons, so that the payoffs of actions are weighted more than their costs. However these two hypotheses have not been yet directly tested in experimental data. This proposal aims at answering the fundamental questions concerning the Go and No-Go neurons: what information do they represent, how this information is integrated during choice and modulated by the activity of neurons releasing dopamine, and how the Go and No-Go neurons learn.We propose to record the activity of Go and No-Go and neurons releasing dopamine while mice make choices between two levers associated with different amounts of reward and effort required to obtain it. In most past experiments studying the activity of the Go and No-Go neurons, their activity was recorded via electrodes inserted into animals' brains, but as the Go and No-Go neurons are intermixed in the brain, it is difficult to identify which of them generate the electrical activity. Therefore, in our study we will use a special technique allowing to record the activity of just one group of neurons. To record the Go neurons we will use special genetically modified mice, in which the Go neurons emit light whenever they produce activity. In these mice only the Go neurons emit light, so the light uniquely signals the activity of Go (rather than No-Go) neurons. To measure this light, two optic fibres will be inserted to two sides of the brain. Two additional groups of animals will be used that produce light during the activity of No-Go and neurons releasing dopamine respectively.We will analyse the activity of Go and No-Go neurons during decision making, and investigate if and how they separately encode payoffs and costs of the options chosen by the animal. We will also study how the activity of neurons releasing dopamine influences decision making. Furthermore, by inspecting the changes in the activity over the experiment we will investigate how the Go and No-Go neurons learn about payoffs and costs of actions. Answering these questions is important because action selection and learning in the basal ganglia are affected in Parkinson's disease and several other disorders. Thus understanding how this system operates in the healthy brain is crucial for development of effective treatments that aim at restoring normal function.