The active place avoidance task characterizes corticohippocampal pathology in Kcnt1 mice

KCNT1 gene mutations are implicated in epileptic and neurodevelopmental disorders. KCNT1 encodes for Slack, a K+ channel expressed in the central nervous system. Slack mutations impair somatostatin-positive interneurons that inhibit corticohippocampal networks. Network disinhibition enables hyperexcitable, hypersynchronous neuronal activity, which precipitates seizures. We hypothesized seizure generation compromise hippocampal function, causing spatial navigation and fear memory deficit. We assessed hippocampal function through the active avoidance task: a mouse placed in a rotating arena with an unmarked shock zone must learn to avoid shocks through environmental cues. Kcnt1 mice received more shocks than wild-type mice, suggesting a Kcnt1-induced hippocampal-dependent learning impairment.