Exaggerated responses to sensory stimuli, a hallmark of fragile X syndrome, contribute to anxiety and learning challenges. Sensory hypersensitivity is recapitulated in the Fmr1 knockout (KO) mouse mod...

Epilepsy is defined as a disorder of the brain characterized by aberrant, excessive neuronal hypersynchrony and an enduring predisposition to epileptic seizures, as defined by the International League Against Epilepsy1. Thus, channelopathies, which mechanistically mediate neuronal networks, have emerged as a critical cause of developmental and epileptic encephalopathies (DEEs), with over 900 identified monogenic etiologies2. DEEs are also associated with a high burden of abnormal epileptiform abnormalities on electroencephalography (EEG), a sign of aberrant neuronal connectivity that results in significant neurodevelopmental delay, and are associated with increased incidence of sudden unexpected death in epilepsy2,3,4. DEEs represent one of the most severe chronic neurological disorders of childhood, requiring complex specialty medical care, frequent emergency room visits and hospitalizations, with consequential socioeconomic impact2,3,4. DEE11 (MIM 613721) is a severe neurodevelopmental disorder caused by gain-of-function (GOF) and mixed-function variants in the SCN2A gene, encoding the neuronal sodium channel NaV1.2 α-subunit. Specific biophysical changes, including alterations in voltage sensing and ion flux, result from individual missense variants, depending on the location and amino acid substitution2. SCN2A GOF variants increase open probability and current flux, resulting in pathophysiologic electrophysiologic changes and neuronal hyperexcitability, with an increased predisposition to seizures early in life4,5. Heterologously expressed SCN2A...

Neuronal hypersynchrony is implicated in epilepsy and other diseases. The low-frequency, spatially averaged electric fields from many thousands of neurons have been shown to promote synchrony. It rema...

Network hypersynchrony is emerging as an important system-level mechanism underlying seizures, as we

Background: Temporal lobe epilepsy (TLE) is associated with severe cognitive impairments including m

Background: Temporal lobe epilepsy (TLE) is associated with severe cognitive impairments including m