Cholinergic Interneurons of the Dorsomedial Striatum Mediate Winner-Loser Effects on Social Hierarchy Dynamics in Male Mice

Abstract

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyThe overall aim of the research reported in this thesis is to investigate the phenomena and putative mechanisms of flexibility in the social hierarchy of male mice (C57BL7/J and heterozygous ChAT-cre mice). 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, when competing with other animals, whether to be a winner or loser, responding to the experience of winning or losing, and subsequent stabilization of rank. The neural circuits underlying such flexible behavior have yet to be fully understood. Previous research indicates that cholinergic interneurons in the dorsomedial striatum play a role in various forms of behavioral flexibility. I hypothesize that similar mechanisms may be involved in social hierarchy dynamics. To investigate the effects of the experience of winning and losing on the social hierarchy, I used the dominance tube test to measure ranking within group housed mice, before and after between-cage competitions using the same test. I 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, I 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. These findings support the concept of winner-loser effects on subsequent competition, and which suggest that cholinergic interneurons in dorsomedial striatum increase the flexibility of social hierarchy dynamics.doctoral thesi