Research articleSemaphorin 6A knockout mice display abnormalities across ethologically-based topographies of exploration and in motor learning

•Genetic disruption of semaphorin-6A produces abnormal exploratory behaviours in a novel environment in mice.•Semaphorin-6A mutant mice show disturbed habituation of exploration in a novel environment.•Heterozygous semaphorin-6A mutants exhibit disruption of motor learning.

Semaphorins are secreted or membrane-bound proteins implicated in neurodevelopmental processes of axon guidance and cell migration. Exploratory behaviour and motor learning was examined ethologically in Semaphorin 6A (Sema6A) mutant mice. The ethogram of initial exploration in Sema6A knockout mice was characterised by increased rearing to wall with decreased sifting; over subsequent habituation, locomotion, sniffing and rearing to wall were increased, with reduced habituation of rearing seated. Rotarod analysis indicated delayed motor learning in Sema6A heterozygous mutants. Disruption to the axonal guidance and cell migration processes regulated by Sema6A is associated with topographically specific disruption to fundamental aspects of behaviour, namely the ethogram of initial exploration and subsequent habituation to the environment, and motor learning.