Dynamic Foraging Behavior Performance Is Not Affected byScn2aHaploinsufficiency

Abstract

AbstractDysfunction in the geneSCN2A, which encodes the voltage-gated sodium channel Nav1.2, is strongly associated with neurodevelopmental disorders including autism spectrum disorder and intellectual disability (ASD/ID). This dysfunction typically manifests in these disorders as a haploinsufficiency, where loss of one copy of a gene cannot be compensated for by the other allele.Scn2ahaploinsufficiency affects a range of cells and circuits across the brain, including associative neocortical circuits that are important for cognitive flexibility and decision-making behaviors. Here, we tested whetherScn2ahaploinsufficiency has any effect on a dynamic foraging task that engages such circuits.Scn2a+/−mice and wild-type (WT) littermates were trained on a choice behavior where the probability of reward between two options varied dynamically across trials and where the location of the high reward underwent uncued reversals. Despite impairments inScn2a-related neuronal excitability, we found that both male and femaleScn2a+/−mice performed these tasks as well as wild-type littermates, with no behavioral difference across genotypes in learning or performance parameters. Varying the number of trials between reversals or probabilities of receiving reward did not result in an observable behavioral difference, either. These data suggest that, despite heterozygous loss ofScn2a, mice can perform relatively complex foraging tasks that make use of higher-order neuronal circuits.