The epileptic brain is distinguished by spontaneous seizures and interictal epileptiform discharges (IEDs). Basic patterns of mesoscale brain activity outside of seizures and IEDs are also frequently disrupted in the epileptic brain and likely influence disease symptoms, but are poorly understood. We aimed to quantify how interictal brain activity differs from that in healthy individuals, and identify what features of interictal activity influence seizure occurrence in a genetic mouse model of childhood epilepsy.
View Article and Find Full Text PDFGain-of-function (GOF) variants in K channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K currents lead to network hyperexcitability. Here, we introduce a human Na-activated K (K) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases K currents in cortical excitatory and inhibitory neurons, there is an increase in the K current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation.
View Article and Find Full Text PDFNeural network function can be shaped by varying the strength of synaptic connections. One way to achieve this is to vary connection structure. To investigate how structural variation among synaptic connections might affect neural computation, we examined primary afferent connections in the olfactory system.
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