Social impairments in mice lacking the voltage-gated potassium channel Kv3.1

• Published in: Behavioural brain research Vol. 413; p. 113468
• Main Authors: Bee, Sarah, Ringland, Amanda, Coutellier, Laurence
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.09.2021
• Subjects: Animals; Autism; Autism Spectrum Disorder - metabolism; Autism Spectrum Disorder - physiopathology; Behavior, Animal - physiology; Behavioral Symptoms - metabolism; Behavioral Symptoms - physiopathology; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Disease Models, Animal; Kv3.1 channel; Mice; Mice, Knockout; Parvalbumin; Parvalbumins - metabolism; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Psychomotor Agitation - metabolism; Psychomotor Agitation - physiopathology; Shaw Potassium Channels - deficiency; Social Behavior; Stereotyped Behavior - physiology; Autism; Mice; Social behavior; Parvalbumin; Kv3.1 channel
• DOI: 10.1016/j.bbr.2021.113468
• ISSN: 0166-4328; 1872-7549

•Mice deficient in the Kv3.1 voltage-dependent potassium channel display social deficits.•Mice deficient in the Kv3.1 channel display hyperactivity.•Mice deficient in the Kv3.1 channel have abnormal expression of parvalbumin in the striatum and prefrontal cortex. Parvalbumin (PV)-expressing neurons have been implicated in the pathology of autism spectrum disorders (ASD). Loss of PV expression and/or reduced number of PV-expressing neurons have been reported not only in genetic and environmental rodent models of ASD, but also in post-mortem analyses of brain tissues from ASD vs. healthy control human subjects. PV-expressing neurons play a pivotal role in the maintenance of the balance between excitation and inhibition within neural circuits in part because of their fast-spiking properties. Their high firing rate is mostly regulated by the voltage-gated potassium channel Kv3.1. It is yet unknown whether disturbances in the electrophysiological properties of PV-expressing neurons per se can lead to behavioral disturbances. We assessed locomotor activity, social interaction, recognition and memory, and stereotypic behaviors in Kv3.1 wild-type (WT) and knockout (KO) mice. We then used Western Blot analyses to measure the impact of Kv3.1 deficiency on markers of GABA transmission (PV and GAD67) and neural circuit activity (Egr1). Deficiency in Kv3.1 channel is sufficient to induce social deficits, hyperactivity and stereotypic behaviors. These behavioral changes were independent of changes in GAD67 levels and associated with increased levels of PV protein in the prefrontal cortex and striatum. These findings reveal that a loss of PV expression is not a necessary factor to induce an ASD-like phenotype in mice and support the need for further investigation to fully understand the contribution of PV-expressing neurons to ASD pathology.