Cerebellum May Drive Addictive Behavior via Dopamine Release

Groundbreaking research unearths previously hidden functions of the cerebellum.

Posted Jan 17, 2019

 Wikipedia/Life Sciences Database
Cerebellum (Latin for "little brain") in red. Cerebellar means "relating to or located in the cerebellum."
Source: Wikipedia/Life Sciences Database

Prior to 1998, when Jeremy Schmahmann of Harvard Medical School published a game-changing landmark paper, “The Cerebellar Cognitive Affective Syndrome”—which identified specific non-motor functions of the human cerebellum for the first time—most neuroscience experts believed that our “little brain” was only involved with motor functions, such as fine-tuning muscle coordination.

In 2007, I published a book, The Athlete’s Way (St. Martin’s Press), that offered practical advice on speculative ways to optimize both motor and non-motor functions of the cerebellum in sports and day-to-day life. Unfortunately, non-motor functions of the cerebellum was still a radically new concept a decade ago. What I thought were visionary ideas were flat-out rejected by the medical establishment and deemed "unrelatable" by most general readers. The book was a total flop, which was disappointing. 

That said, for the past ten years, I’ve woken up every morning hoping to find more empirical evidence that supports the hypothesis that our "little brain" is involved in both motor and non-motor functions. As a blogger, I’ve done my best to report on every significant finding regarding the mysterious cerebellum and to maintain a one-stop-shop chronological timeline of early-21st century cerebellar research for posterity. (See here, here, here, here, and here.)

Suffice to say, I almost fell off my chair this morning when I read an embargoed press release, “The Cerebellum's Hidden Roles in Social and Reward-Driven Behavior,” from the American Association for the Advancement of Science announcing a new study (Carta et al., 2019) being published online January 17th in the journal Science.

This first-of-its-kind study on mice reports that the cerebellum may regulate reward-driven behaviors (such as addiction) and sociability by controlling the release of dopamine

For their recent paper on previously hidden roles of the cerebellum, “Cerebellar Modulation of the Reward Circuitry and Social Behavior,” co-first authors Ilaria Carta and Christopher Chen (who is currently a postdoctoral fellow at Harvard Medical School's Department of Neurobiology) along with colleagues at the Albert Einstein College of Medicine investigated a possible link between the cerebellum and reward-processing behavior in the brains of mice using optogenetics.

Carta and Chen's research team at Einstein was led by senior author, Kamran Khodakhah, who is the founder and director of the Kam Lab, which focuses on the cerebellum’s role in motor coordination as well as non-motor cerebellar functions relating to social behaviors and addiction.

Before reading further, please take a few minutes to watch this highly informative (and visually stunning) video of Kamran Khodakhah describing his Lab’s process of exploring how the cerebellum plays a role in social and reward-driven behavior using state-of-the-art techniques:

In the study abstract, Ilaria Carta, Chris Chen, and their co-authors explain some significant scientific details about discovering that the cerebellum may regulate reward-driven behavior and sociability by controlling dopamine release:

"The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior." 

In an accompanying Perspective piece, “The Cerebellum Gets Social,” Egidio D’Angelo from the Department of Brain and Behavioral Sciences at the University of Pavia in Italy (who was not involved in the recent study by Carta et al.) sums up the importance of discovering that the cerebellum may be involved in the regulation of social and reward-driven behaviors via dopamine release. D’Angelo writes:

“On page 248 of this [Science Vol. 363 Issue 6424] issue, Carta et al. (2019) show that the cerebellum can activate the ventral tegmental area (VTA). The VTA is a mesencephalic nucleus giving rise to the mesocortical and mesolimbic fiber bundles that release dopamine to the prefrontal cortex and ventral striatum. Dopamine, in turn, plays a fundamental role in cognitive and emotional functioning by regulating motivation and reward. This places the cerebellum into the main circuits regulating brain states and social behavior.

Carta et al. suggest that dysfunction of the cerebellum-VTA connection could contribute to the pathogenesis of diseases in which the dopaminergic system is dysregulated, including ASD and schizophrenia (15), and to conditions such as drug addiction. These proposals need critical validation in humans. This study opens a new avenue for interpreting the function of the cerebellum and also for understanding social behavior and related pathologies, with the potential to discover novel therapies to treat these diseases.”

Immediately after reading about the new study by Carta et al. this morning, I was curious to learn more directly from the senior author. In an email correspondence I wrote, "Kamran Khodakhah, could you summarize the significance of your team's latest paper, "Cerebellar Modulation of the Reward Circuitry and Social Behavior," which unearths previously underappreciated non-motor functions of the cerebellum, for the general Psychology Today reader?" Khodakhah responded: 

“Containing more than half the neurons in our brain, historically cerebellum has been perhaps one of its most underappreciated regions. In the past, we have dogmatically ignored evidence in support of the notion that in addition to contributing to motor coordination cerebellum has a rich repertoire of cognitive, affective, and social functions. One reason for this stance has been the absence of known direct connections between the cerebellum and brain regions that control our non-motor behaviors. The finding that cerebellum sends powerful projections to the ventral tegmental area, a dopaminergic brain center responsible for reward processing and essential for a myriad of behaviors, provides a framework for thinking about non-motor cerebellar functions. I have no doubt that further connections between the cerebellum and other non-motor brain regions will be unearthed in the coming years.”

We are living in a thrilling era of unprecedented cerebellar discovery. Almost once a month, it seems another groundbreaking study is published that sheds light on aspects of the cerebellum that have been hidden and completely unfathomable until now.

If you'd like to keep your finger on the pulse of all the latest research regarding the "little brain," I'd recommend creating Google Alerts for the words "cerebellum" and "cerebellar." 

References

Ilaria Carta, Christopher H. Chen, Amanda L. Schott, Schnaude Dorizan, and Kamran Khodakhah. "Cerebellar Modulation of the Reward Circuitry and Social Behavior." Science (First published online: January 17, 2019) DOI: 10.1126/ science.aav0581

"The Cerebellum Gets Social" Perspective piece by Egidio D’Angelo. Science (First published online: January 17, 2019) DOI: 10.1126/science.aaw2571

Jeremy D. Schmahmann and Janet C. Sherman. "The Cerebellar Cognitive Affective Syndrome." Brain: A Journal of Neurology (First published: April 1, 1998) DOI: 10.1093/brain/121.4.561

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