Sabrina Petri

Abstract Identifying and quantifying synchronous activity of primary neuronal networks using multielectrode arrays (MEAs) can potentially provide a medium-throughput platform to screen potential therapeutics for genetic epileptic encephalopathies (EEs). However, successfully identifying screenable synchrony phenotypes in vitro poses significant experimental and analytical challenges.

Highlights • In humans, KCNT1 GOF variants cause severe epilepsy and intellectual disability • KCNT1 GOF increases subthreshold KNa currents selectively in GABAergic neurons • KCNT1 GOF impairs GABAergic neuron excitability and alters synaptic connectivity • Mice expressing a Kcnt1 GOF variant exhibit seizures and cognitive impairments Summary Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead...