Cholinergic interneurons of the dorsomedial striatum mediate winner-loser effects on social hierarchy dynamics in male mice.

Abstract

Cholinergic interneurons of the dorsomedial striatum may play a role in social hierarchy dynamics. A social hierarchy is an organization of individuals by rank that occurs in social animals. Establishing a new social hierarchy involves flexible behavior in deciding whether to be a winner or loser, experience of winning or losing, and stabilization of rank. The neural circuits underlying such flexible behavior have yet to be fully understood, but previous research indicates that cholinergic interneurons in the dorsomedial striatum play a role in behavioral flexibility. We used the dominance tube test to measure ranking within group housed mice, before and after between-cage competitions using the same test. We found that the experience of winning or losing against mice from different cages not only contributes to new social hierarchies among the competitors, but also causally influences the subsequent social hierarchy among their cage mates in the home cage - supporting the hypothesis of winner-loser effects on later social ranking. To test the hypothesis that cholinergic interneurons contribute to social hierarchy dynamics, we made a selective lesion of cholinergic interneurons in the dorsomedial striatum. The lesion did not prevent social hierarchy formation among pairs of similarly ranked individuals from different cages. However, it reduced the loser effect of external competition on the subsequent home-cage rankings in dominant mice. In light of these results we suggest that cholinergic interneurons in dorsomedial striatum increase the flexibility of social hierarchy dynamics. Significance statementThe effect of winning or losing a competition on subsequent ranking in mouse home cage social hierarchies was examined using the dominance tube test. We found that losing, when dominant mice were defeated by equally ranked mice from another cage, led to decreased social rank in their home cage. Conversely, winning by initially subordinate mice led to increased rank in the home cage social hierarchy. The loser effect on subsequent behavior in dominant mice was reduced after selective lesions of the cholinergic interneurons of the dorsomedial striatum. We suggest that losing might produce these effects by altering the activity of cholinergic interneurons, and thus modulating synaptic plasticity in neural circuits involved in flexible decision making and positive reinforcement.