Neuronal Kv7/
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 Kv7.2 and Kv7.3 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 (KCNQ2) and
Potassium Voltage-Gated Channel Subfamily Q Member 3 (KCNQ3) genes are associated with
benign familial neonatal epilepsy (BFNE) in which most
seizures spontaneously remit within months without cognitive deficits. De novo mutations in KCNQ2 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 KCNQ2 is recently shown to induce spontaneous
seizures and cognitive deficit in mice, although it is unclear whether this cognitive deficit is caused directly by Kv7 disruption or by persistent
seizures in the developing brain as a consequence of Kv7 disruption. In this study, we examined the role of Kv7 channels in learning and memory by behavioral phenotyping of the KCNQ2+/- mice, which lack a single copy of KCNQ2 but dos not display spontaneous
seizures. We found that both KCNQ2+/- 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 KCNQ2 has minimal effects on learning or memory in mice in the absence of spontaneous
seizures.