Abstracts

Rationale: Psychiatric comorbidities are common in epilepsy, yet the genes, mechanisms, and neural networks remain unclear. One gene of interest is Kcna1, encoding Kv1.1 potassium channels, key regulators of neuronal excitability. Loss of Kv1.1 function is associated with epilepsy and episodic ataxia. Recently, heterozygous Kcna1^+/- mice, while seizure-free, exhibit repetitive behaviors and reduced sociability, resembling autism-like traits observed in Scn2a^+/- mice, a recognized autism model. These findings suggest Kv1.1 dysfunction may contribute not only to epilepsy but also to psychiatric conditions such as autism, anxiety, and depression. To test this, we assessed neurobehavioral deficits in two Kcna1 channelopathy models: 1) mice with null Kcna1 alleles (-) associated with epilepsy; and 2) mice with a missense Kcna1 mutation (V408A) linked to episodic ataxia.

Methods: Standard behavioral assays were run to identify psychiatric phenotypes in age-matched, juvenile (4-5 weeks old) Kcna1^-/-, Kcna1^+/-, and Kcna1^V408A/+mice (8-20 mice/genotype per test). Scn2a^+/- mice were used as positive controls and WT littermates as negative controls. Depressive-like behaviors were assessed with tail suspension and forced swim tests. Sociability was evaluated using the olfactory habituation/dishabituation test. Anxiety-like behaviors were assessed using the open field and marble burying tests. Data were analyzed in GraphPad Prism software using 1-way ANOVA or paired t-tests, as appropriate, with P< 0.05 for significance.