7α-Hydroxypregnenolone, a key neuronal modulator of locomotion, stimulates upstream migration by means of the dopaminergic system in salmon

Salmon migrate upstream against an opposing current in their natal river. However, the molecular mechanisms that stimulate upstream migratory behavior are poorly understood. Here, we show that 7α-hydroxypregnenolone (7α-OH PREG), a newly identified neuronal modulator of locomotion, acts as a key factor for upstream migration in salmon. We first identified 7α-OH PREG and cytochrome P450 7α-hydroxylase (P450(7α)), a steroidogenic enzyme producing 7α-OH PREG, in the salmon brain and then found that 7α-OH PREG synthesis in the brain increases during upstream migration. Subsequently, we demonstrated that 7α-OH PREG increases upstream migratory behavior of salmon. We further found that 7α-OH PREG acts on dopamine neurons in the magnocellular preoptic nucleus during upstream migration. Thus, 7α-OH PREG stimulates upstream migratory behavior through the dopaminergic system in salmon. These findings provide new insights into the molecular mechanisms of fish upstream migration.