Heterozygous Deletion of Epilepsy Gene Has Negligible Effects on Learning and Memory.

Neuronal K7/Potassium Voltage-Gated Channel Subfamily Q (KCNQ) potassium channels underlie M-current that potently suppresses repetitive and burst firing of action potentials (APs). They are mostly heterotetramers of K7.2 and K7.3 subunits in the hippocampus and cortex, the brain regions important for cognition and behavior. Underscoring their critical roles in inhibiting neuronal excitability, autosomal dominantly inherited mutations in Potassium Voltage-Gated Channel Subfamily Q Member 2 () and Potassium Voltage-Gated Channel Subfamily Q Member 3 () genes are associated with benign familial neonatal epilepsy (BFNE) in which most seizures spontaneously remit within months without cognitive deficits. mutations in also cause epileptic encephalopathy (EE), which is characterized by persistent seizures that are often drug refractory, neurodevelopmental delay, and intellectual disability. Heterozygous expression of EE variants of is recently shown to induce spontaneous seizures and cognitive deficit in mice, although it is unclear whether this cognitive deficit is caused directly by K7 disruption or by persistent seizures in the developing brain as a consequence of K7 disruption. In this study, we examined the role of K7 channels in learning and memory by behavioral phenotyping of the 2 mice, which lack a single copy of but dos not display spontaneous seizures. We found that both 2 and wild-type (WT) mice showed comparable nociception in the tail-flick assay and fear-induced learning and memory during a passive inhibitory avoidance (IA) test and contextual fear conditioning (CFC). Both genotypes displayed similar object location and recognition memory. These findings together provide evidence that heterozygous loss of has minimal effects on learning or memory in mice in the absence of spontaneous seizures.