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Title: Heterozygous Deletion of Epilepsy Gene KCNQ2 Has Negligible Effects on Learning and Memory

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 novomutations inKCNQ2also 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 ofKCNQ2is 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 theKCNQ2+/−mice, which lack a single copy ofKCNQ2but dos not display spontaneous seizures. We found that bothKCNQ2+/−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 ofKCNQ2has minimal effects on learning or memory in mice in the absence of spontaneous seizures.

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Award ID(s):
1735252
NSF-PAR ID:
10471623
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Frontiers
Date Published:
Journal Name:
Frontiers in Behavioral Neuroscience
Volume:
16
ISSN:
1662-5153
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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