Cerebellum connects to brain’s reward system

At a Glance Researchers found that the brain’s cerebellum—known to play a role in motor coordination—also helps control the brain’s reward circuitry.

These findings in mice shed new light on brain circuits that are critical to behaviors commonly seen with substance use disorders and psychiatric disorders.

Thomas Deerinck, National Center for Microscopy and Imaging Research, University of California, San Diego

The cerebellum plays a well-recognized role in the coordination and regulation of motor activity. Recent research suggests that this brain area also contributes to a host of non-motor functions. For example, brain activity in the cerebellum has been linked to motivation, social and emotional behaviors, and reward learning. Each of these can be disrupted in psychiatric disorders. Abnormalities in the cerebellum have been linked to autism, schizophrenia, and substance use disorders.

The ventral tegmental area (VTA) of the brain is an important area of the brain’s reward system and for controlling motivational behaviors. A team led by Dr. Kamran Khodakhah at Albert Einstein College of Medicine explored whether there is a direct connection between the cerebellum and the VTA. They carried out a series of experiments using a technique called optogenetics. This approach allows genetically modified brain cells in the mouse cerebellum to be controlled using pulses of light. The research was supported in part by several NIH components, including the National Institute of Mental Health (NIMH). Results were published on January 18, 2019, in Science.

The researchers found that activating brain cells in the cerebellum led to increased activity in the VTA. They then tested whether activating or inactivating these brain cells influenced reward-related or social behaviors in the mice.

The team placed mice in an open-field chamber that was divided into four sections. The mice preferred to spend time in the area where they received light-induced activation of the cerebellum. The animals were even willing to spend time in conditions they usually don’t prefer—such as a brightly lit area—after they learned to associate it with the brain stimulation. This suggests that stimulating these connections was rewarding in and of itself.

The researchers next tested the mice in a social task. Mice could choose to spend time in a chamber with another mouse (social chamber), in an empty central chamber, or in a chamber containing an object. The animals normally preferred to be in the social chamber. But after researchers turned off the cerebellum-VTA connections, the mice no longer showed this preference. Further experiments revealed that these brain cells became more active in the presence of another mouse. The findings suggest that these connections serve to activate the reward system in social situations.

“This type of research is fundamental to deepening our understanding of how brain circuit activity relates to mental illnesses,” says NIMH director Dr. Joshua A. Gordon. “Findings like the ones described in this paper help us learn more about how the brain works, a key first step on the path towards developing new treatments.”