How the Human Cerebellum's Evolution Makes Our Brains Unique

Purkinje cells were discovered by Jan Evangelista Purkyně in 1839 and famously illustrated by Santiago Ramón y Cajal in 1899. This Ramón y Cajal drawing shows cerebellar Purkinje cells (A) and granule cells (B) in the pigeon cerebellum.

Source: Instituto Santiago Ramón y Cajal, Madrid, Spain/Public Domain

Purkinje cells (PCs) are unique fan-shaped neurons found only in the cerebellum. PCs facilitate well-coordinated movements and help the brain automatically make quick course corrections when a movement goes wrong or something unexpected happens, such as slipping or losing your balance. In this way, Purkinje cells protect us from accidents and other mishaps that could cause bodily harm or even death.

Throughout the 20th century, Purkinje cells were viewed primarily as the seat of muscle memory because they help athletes and others who perfect physically coordinated motions move lots of different muscles synchronistically without overthinking the process. The fluidity of graceful, perfectly coordinated movement relies on the cerebellum's Purkinje cells.

More recently, accumulating 21st-century evidence suggests that in addition to coordinating voluntary muscle movements, the cerebellum's Purkinje cells may also play a role in coordinating neuronal communication in the cerebral cortex associated with human thinking processes. (See "The Neuroscience of Superfluid Thinking")

Purkinje Cell Evolution Makes the Human Cerebellum Unique

New research (Sepp and colleagues, 2023) from Heidelberg University's Center for Molecular Biology in Germany traces evolutionary differences in the cellular development of the mammalian cerebellum in humans, mice, and opossums. These findings were published on November 29 in the peer-reviewed journal Nature.

For this study, senior author Henrik Kaessmann and colleagues generated single-nucleus RNA-sequencing data for about 400,000 cells in each species' cerebellum and created genetic maps that reveal unique species-specific cerebellar characteristics that span over 160 million years of mammalian brain evolution.

Cerebellum in orange. The magnified close-up view is of a human cerebellar Purkinje cell.

Source: Kateryna Kon/Shutterstock

"Although the cerebellum, a structure at the back of the skull, contains about 80 percent of all neurons in the whole human brain, this was long considered a brain region with a rather simple cellular architecture," Kaessmann said in a news release. "In recent times, however, evidence suggesting a pronounced heterogeneity within this structure has been growing."

The Kaessmann Lab's latest (2023) cross-species analysis of the mammalian cerebellum reveals broadly conserved developmental dynamics of different cerebellar cells across species, except when it comes to Purkinje cells, which appear to have gone through a unique evolutionary expansion in the human lineage over the past 160+ million years.

Additionally, the researchers identified over 1,000 genes in the mammalian cerebellum that have different activity profiles in humans, mice, and opossums. "At the level of cell types, it happens fairly frequently that genes obtain new activity profiles. This means that ancestral genes, present in all mammals, become active in new cell types during evolution, potentially changing the properties of these cells," co-author Kevin Leiss explains.

Human Purkinje Cell Expansion May Support Our Intellectual Capacities

The researchers speculate that this Purkinje cell activity profile and robust expansion were driven by specific subtypes of PCs seen only in the human brain that are generated during early fetal development and forge communication pathways with neocortical cerebral areas involved in both motor movements and non-motor cognitive functions as the human brain matures.

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"It stands to reason that the expansion of these specific types of Purkinje cells during human evolution supports higher cognitive functions in humans," first author Mari Sepp concluded in the Heidelberg University news release.

More research is needed to pinpoint how the evolutionary expansion of Purkinje cells over millions of years supports modern-day human intelligence and if finding ways to enhance Purkinje cells' functionality in our daily lives can boost overall brain power and improve cognitive performance.