Scientists have uncovered a previously unknown mechanism by which inherited mutations in calcium channels disrupt brain development at a very early stage, increasing children’s susceptibility to epilepsy and related cognitive problems. The findings, published in the journal Neuron, provide new insight into how even minor genetic changes can affect brain networks long before the first seizures appear.

The researchers focused on so-called P/Q-type calcium channels, which play a key role in regulating the release of neurotransmitters—the chemical signals that allow nerve cells to communicate. Although mutations in these channels had previously been linked to childhood epilepsy, the exact mechanisms affecting the formation of neural circuits remained unclear.

To investigate this, a team led by graduate student Samantha Thompson and Dr. Qing-Long Miao used a mouse model of childhood absence epilepsy—a form of the disorder that begins in early childhood and is characterized by specific patterns of brain activity.

The scientists found that reduced function of P/Q-type channels not only impairs neurotransmitter transmission but also unexpectedly increases the excitability of the thalamus, a brain region involved in consciousness, attention, and sensory processing. Moreover, the mutant calcium channel activated the Wnt signaling pathway, which promotes excessive division of thalamic neurons.

This led to abnormally high cell proliferation even before birth, suggesting that the roots of epilepsy may lie in prenatal development much earlier than the onset of seizures.

In addition, the mutation significantly increased the expression of two genes previously known to trigger epilepsy, which may help explain why standard single-drug therapies are often ineffective in such patients.

According to experts, these findings open new possibilities for early diagnosis and more targeted therapies that take into account both abnormal neuronal excitability and disruptions in developmental signaling pathways.

Understanding how these genetic and cellular mechanisms interact could ultimately lead to more effective treatments for epilepsy and related neurodevelopmental disorders in children.