Cerebellar granule cells, which make up the cerebellum, are the smallest and most abundant of all neuron types in the brain. These cells are known to contribute to motor function, attention, language, and fear. A recent study published in Nature demonstrates that these cells may also contribute to our expectations of whether a given action will result in a positive reward. It's a discovery that departs from our previous understanding of how these types of cells function.

To examine the function of these cerebellar granule cells, the authors used a mouse model of reward and reward anticipation. In this model, mice are trained to push a lever to receive a small treat of sugar-water.

When the authors looked directly at the electrical activity in the brains of these mice, they saw that some of these cerebellar granule neurons were activated throughout the lever-pushing task. The peak of neuronal activity coincided with the peak of physical activity for up to 20 percent of the cells. However, not all populations of cells fired during the same part of the lever-pushing task, so the researchers wanted to learn more about the neuronal differences among these subpopulations of cells.

Is that rewarding?

The authors in Nature found that some of the cells fired preferentially before reward delivery. Other cells, meanwhile, had larger responses when the mice pushed the lever and did not receive the expected sugar-water reward (called an "omitted reward"). The authors went on to study these two types of cells separately—the cells that were responsive to reward omission and those that were firing just prior to receiving a reward.

When they looked at the cell-response distribution in the mouse cerebellum during the handle-pushing task, the researchers saw that approximately 5 percent of the neurons fired in response to reward, 12 percent were fired with reward omission, and 9 percent were firing in reward anticipation. A similar distribution of neuronal responses was found when mice were trained in a completely different reward task, which suggests that those cells were not involved in the lever-pushing activity. Instead, this distribution of cells is common across mice and is generally involved in reward-associated tasks.

The authors then looked at the neuron firing more closely. They tracked the activity of individual neurons as the mice were learning to complete reward tasks. After six days of training, they saw that neurons with the strongest reward-anticipation responses were the same neurons that had responded only after a reward was delivered while the mice were in training. This suggests that the role of those neurons shifts from recognizing a treat to anticipating one.

The neurons that responded most strongly to reward omission at the end of training were the same neurons that responded to reward omission earlier in the training. Again, these observations suggest that the cerebellar granule neurons are specialized in terms of their responses to reward or lack of reward.

This paper contributes new information to neuroscience's understanding of how we respond to rewards. It shows that neurons are specialized to fire during different parts of a reward-related task: some neurons respond strongly in anticipation, others fire when they get the expected reward, and another group activates when the reward doesn't show up. As neuroscientists continue to characterize the brain, the synthesis of this type of function-specific finding should eventually help to build a big picture of how different brain regions interact and function.

Nature, 2017. DOI: 10.1038/nature21726 (About DOIs)