How dopamine signals in the “little brain” boost sociability


This illustration highlights the cerebellum (Latin: “little brain”) with a close-up view of Purkinje cells, one of the most distinctive types of neurons in the cerebellar cortex. Cerebellar means “pertaining to the cerebellum”.

Credit: Kateryna Kon/Shutterstock

Before the publication of a game-changing article Brain paper by Jeremy Schmahmann and Janet Sherman of Harvard’s Massachusetts General Hospital in 1998, most neuroscientists thought of the cerebellum as a purely motor brain region that coordinated muscle movement but had nothing to do with cognition or social behaviors.

For example, as a beginner tennis player in the 1970s, my neuroscientist father, who also worked at Harvard Medical School, trained me on the weekends and incorporated cerebellar functions into my tennis lessons. Dad taught me how Purkinje cells in the cerebellum hold muscle memory and help athletes excel in sports by allowing them to hit home runs, kick field goals, and serve aces without consciously thinking about every movement.

As a tennis coach, Dad knew that peak performance on the court was more likely if a player trained the so-called “little brain” to perform precise muscle movements with automation. He also knew that optimizing cerebellar functions facilitated superfluidity (a state of frictionless flow) and made it less likely that a tennis player would choke due to overthinking every stroke.

Also, since my father was both a neuroscientist and a neurosurgeon, his metacognitive knowledge of the role Purkinje cells played in muscle memory and not choking gave him grace under pressure when he operated on other people’s brains. Just as “practice, practice, practice” improved his cerebellum’s ability to serve aces and avoid unforced errors on the tennis court, Dad also credited optimizing cerebellar function with deserves credit for making him a better brain surgeon in the operating room.

As a brain surgeon in the 20th century, my father operated on people who had cerebellar lesions, tumors, or damage to different parts of the cerebellum. During the 1970s, 1980s and 1990s he noticed that in some patients cerebellar abnormalities did not seem to affect motor functions, but affected them in other ways. Because no one thought the cerebellum was involved in non-motor functions at the time, these observations were puzzling.

The role of the cerebellum in social cognition remains a mystery

When dad served as a medical consultant for my book The athlete’s way in 2005 he encouraged me to shed light on the cerebellum and Purkinje cells because of their well-established role in motor processes and athletic mastery of complex motor sequences.

Furthermore, based on his first-hand observation of cerebellar abnormalities affecting social and emotional processes and the accumulation of evidence-based research, he also advised that all brain maps of cerebro-cerebellar circuits included in the book should represent that the cerebellum was not just a cerebral center of motor function only.

That said, at the time, no one really knew that different regions of the cerebellum and cerebellar microzones were involved in motor and non-motor functions. The way Dad summed up all the cerebellar unknowns circa 2005 was to say, “We don’t know exactly what the cerebellum does, but whatever it does, it does a lot.”

It wasn’t until around 2015 that neuroscientists began to focus on how different regions and microareas of the cerebellum play a role in social cognition.

“Research on the relationship between the cerebellum and social cognition is very young, and apart from occasional early contributions, has begun to emerge over the past five years,” Frank Van Overwalle and Mario Manto said. wrote in 2020. “Previous reports on the social role of the cerebellum were often limited to secondary aspects of affective processing and anecdotally described cerebellar patients with affective deficits.”

    Mosconi et al., Frontiers in Neuroscience (2015)/CC BY 4.0

Posterior view of the human cerebellum, showing the cerebellar fissure, lobular organization, and deep nuclei embedded in the cerebellar cortex.

Source: Mosconi et al., Frontiers in Neuroscience (2015)/CC BY 4.0

Dopamine D2 receptors in the cerebellum may regulate social behavior

Over the past decade, neuroscientists have attempted to determine how the cerebellum influences social behavior in humans and animals.

A new animal study (Cutando et al., 2022) by an international team of researchers sheds light on how dopamine D2 receptors (D2Rs) regulate social behavior in mice. These results were published June 16 in the peer-reviewed journal Natural neuroscience.

“We discovered an unexpected causal link between Purkinje cells” [dopamine] D2R expression levels right in the center of the cerebellum, Crus I/II lobules, and modulation of social behaviors,” said first author Laura Cutando of the Universitat Autònoma de Barcelona (UAB) in a June 2022 Press release.

“Reduced expression of this specific dopamine receptor impaired the mice’s sociability as well as their preference for social novelty, while their coordination and motor functions remained unchanged,” she writes.

Cutando et al. used genetic tools and different mouse models to investigate how altering D2R levels in cerebellar Purkinje cells could alter social behaviors without affecting motor functions. By selectively altering dopamine D2 signaling in mouse Purkinje cells, the researchers were able to analyze how underexpression and overexpression of D2Rs affected motor and non-motor cerebellar functions. As mentioned, reducing dopamine D2R expression levels made the mice less social, while increasing D2R signaling increased sociability.

According to the researchers, these findings could pave the way for a better understanding of how dopamine signaling in the cerebellum plays a role in psychiatric conditions such as schizophrenia, attention deficit/hyperactivity disorder (ADHD) and generalized anxiety disorder (GAD). Of course, human studies are needed to identify how cerebellar dopamine D2 receptors regulate social behaviors in people.


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