Misdirected nerve cells throw the brain out of sync

If nerve cells do not migrate to the right place during brain development, periventricular heterotropy occurs. This is a disorder that is often associated with seizures and learning difficulties. An international team led by Professor Silvia Cappello, research group leader at LMU's Biomedical Center and member of the SyNergy Cluster of Excellence, has now investigated the properties of these misplaced nerve cells and found an explanation for their hyperactivity.

The researchers used stem cells from patients with periventricular heterotrophy to grow a three-dimensional miniature brain model, a so-called cerebral organoid, and investigated the functioning of the neuronal network in the organoid. They found that affected nerve cells are easier to excite and show greater electrical activity. In particular, mutations in a specific gene (DCHS1) lowered the stimulation threshold of these nerve cells. In addition, it was found that these nerve cells have a more complex morphology and altered synaptic connections to their neighbors. This could explain why they are overactive. The researchers were able to reverse this overactivity using the antiepileptic drug lamotrigine

"Our findings provide new insights into how the brain's connectivity is disrupted," says Cappello. "They could help to explain some of the neurological impairments associated with the disease and open up new treatment approaches for affected people in the long term."

F. Di Matteo et al.: Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopia. Nature Communications 2025