A new study by McGill University researchers yields insights into how the disruption of calcium transport in the brain is linked to autism and intellectual disability. The findings, published in the journal Nature, not only upend a long-held belief among neuroscientists, but could pave the way for treatments.
The researchers discovered that tiny protein structures on brain cells, known as AMPA receptors, can transport calcium. While previous research had suggested that disruptions in calcium signalling might be linked to neurological disorders, the specific role of AMPA receptors in transporting calcium and how mutations in these receptors contribute to autism and intellectual disability had not been established, said senior author Derek Bowie, Professor in McGill's Department of Pharmacology and Therapeutics.
"Most people know calcium is vital for bone health, but in the brain, calcium is a critical signalling molecule that controls learning and memory. Our study is the first to show that when calcium transport through AMPA receptors is disrupted, it can lead to autism and intellectual disability," Bowie said.
"More importantly, it offers a new direction for therapeutic strategies aimed at correcting these calcium imbalances," he said.
Rewriting the science of learning and memory
For over 30 years, scientists believed that AMPA receptors couldn't transport calcium, a conclusion made long before the discovery of "helper" proteins that interact with these receptors in the brain. To the researchers' surprise, no one had revisited this assumption until now.
To challenge the current theory, the McGill team recreated AMPA receptors in the lab, incorporating these helper proteins to mimic their natural state in the brain. The experimental data was then modelled by the lab of Anmar Khadra, Professor in McGill's Department of Physiology. Together, they discovered AMPA receptors are not only capable of transporting calcium, but their ability to do so is far greater than previously thought.
"Our discovery means that all textbooks about this brain function will have to be rewritten to take our findings into account," said Bowie.
Beyond autism and intellectual disability, AMPA receptors play a role in a range of neurological disorders, including ALS, glaucoma, dementia and glioblastoma multiforme brain cancer, the researchers said. This breakthrough opens the door to drug development that targets AMPA receptors, offering hope for patients with these conditions.
About the study
"GluA2-containing AMPA receptors form a continuum of Ca2+-permeable channels" by Federico Miguez-Cabello and Derek Bowie et al. was published in Nature.
The study was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, Fonds de recherche du Québec, the CureGRIN foundation and the Syngap Research Fund.
