Scientists shed light on what makes human neurons function differently from those of other animals
December 22, 2023
Leuven, 22 December – Ever wondered what sets our human brain apart from our primate relatives? Now, scientists led by Baptiste Libé-Philippot, Joris De Wit, and Pierre Vanderhaeghen at the VIB-KU Leuven Center for Brain & Disease Research discovered a piece of this puzzle. They identified a gene that is selectively expressed in human neurons and plays a pivotal role in regulating electrical excitability, a fundamental aspect of brain function that can be disrupted in neurological alterations such as epilepsy and autism. The study, published in Cell, sheds light on the evolution of the human brain and advances our understanding of neurological disorders.
King of the brain jungle
Humans display higher cognitive functions compared to the rest of the animal kingdom, with increased performance in language, abstract reasoning, and social cognition. But what actually sets the human brain apart from other species? Human brain specificity is linked to the evolution of our neural circuits, just like the performance of a computer can be improved by modifying the wiring of the microcircuits. But scientists recently found that the functional processing units of our brain - the neurons - have also evolved in our species.
One important human characteristic lies in the electrical properties of neurons in the cerebral cortex, the outer layer of the brain responsible for higher-order cognitive functions. Compared to other species, human cortical neurons are less excitable, thus generating fewer electrical signals in response to the same stimuli. Electrical signals are crucial for neuronal communication, whereby reduced excitability in human cortical neurons could enable them to process more complex information. However, what makes human neurons less excitable is still unknown. Now, researchers from VIB have discovered a piece of the puzzle.
“We discovered a novel gene that modulates the excitability of neurons of the human brain, but not of other species,” says Professor Pierre Vanderhaeghen. “This finding suggests that some of our neurons may function differently from those of other primates, even chimpanzees. This was quite unexpected from what we know so far about human evolution.”
Deciphering the neuronal landscape
In their latest study, the scientists discovered a receptor protein called LRRC37B that is present and selectively active in neurons of the human cerebral cortex but not in those of other animals, including chimpanzees. By interacting with other proteins, LRRC37B modulates the activity of the neurons’ electric currents, thereby regulating how our neurons transmit signals. The researchers further demonstrated that neurons from human brain tissue that expressed LRRC37B were less excitable than neurons that did not express the receptor.
“Our findings suggest that our human ancestors acquired the expression of the LRRC37B gene during evolution, which regulates our neuronal physiology,” explains Dr. Baptiste Libé-Philippot, first author of the study. “The results show that LRRC37B contributes to the lower excitability of the neurons of the human cerebral cortex, a feature that may contribute to our enhanced cognitive abilities. For instance, this might enable us to process more complex information with greater efficiency and precision, such as processing language.”
From evolution to therapy
The discovery of LRRC37B is not only significant for the study of the brain but also for brain diseases and their treatments. Indeed, the researchers discovered that the LRRC37B protein acts in neurons by interacting with several other proteins, which are all involved in severe forms of epilepsy and autism, and these diseases are associated with abnormal neuronal excitability.
Professor Vanderhaeghen is looking forward to the future: “LRRC37B stands out as an attractive drug target. By manipulating its signaling through medication, it may be possible to modulate neuronal excitability, which could be useful for many neurological disorders. Thus, we hope that, by understanding human brain evolution better, we may find innovative treatments for human brain diseases.”
Publication
LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons. Libé-Philippot et al. Cell, 2023. DOI: 10.1016/j.cell.2023.11.028
This work was funded by the European Research Council, the EOS/FWO Program, the FWO, the Generet Foundation, and the Belgian Queen Elizabeth Foundation.
About the VIB-KU Leuven Center for Brain & Disease Research
Scientists at the VIB-KU Leuven Center for Brain & Disease study how brain cells are organized and how they communicate with each other. These mechanisms reveal and provide insights into what goes wrong in brain diseases such as Alzheimer's, Parkinson's, ALS, and dystonia. This basic work should ultimately lead to new drugs for use against these currently incurable diseases.
About KU Leuven
KU Leuven is Europe’s most innovative university (Reuters) and ranks 45th in the Times Higher Education World University Rankings. As Belgium's largest university, KU Leuven welcomes 60,000 students from over 140 countries. Its 7,000 researchers are active in a comprehensive range of disciplines. KU Leuven is a founding member of the League of European Research Universities (LERU) and has a strong European and international orientation. University Hospitals Leuven, its network of research hospitals, provides high-quality healthcare and develops new therapeutic and diagnostic insights with an emphasis on translational research.