Habenula in mammals is divided into the medial (MHb) and lateral (LHb) parts with independent connectivity, and MHb is further subdivided into the dorsal (dMHb) and ventral (vMHb) subregions. During animal conflicts, previous winning or losing experiences influence the result of following contests, individuals with winning experience tend to win or defeated ones show the higher probability to lose in the next fight (winner or loser effect). Zebrafish also exhibit these effects, and zebrafish with the silenced lateral subnulceus of dorsal habenula, corresponding to dMHb in manmals, showed impaired accumulation of confidence and higher tendency to lose in the fights. We hypothesized that both dMHb and vMHb in mice are related to aggression behaviors but they work agonistically.
vMHb projects to the interpeduncular nucleus (IPN) and previous reports showed that neurons in vMHb include both glutamate (Glu) and acetylcholine (ACh) as transmitters. We developed the mice in which ACh transmission was selectively inhibited only in the vMHb-IPN circuit and examined their conflict behaviors. ICR mice are normally larger and stronger than B6 mice. Using ICR mice as opponent, we performed the tube test (the test of defining that which mouse is higher lank of two) and found Ach-inhibited mice showed higher tendency to win even if opponent ICR mice were larger than them. Next, using C3H mice, which are basically modest than B6, as an intruder, we performed resident-intruder-paradigm test (RIP). Ach-inhibited mice exhibited more dominant aggressive behaviors and received less attacks from intruders than control mice. Now we are examining the mechanisms as to why Ach-inhibited mice are stronger and more aggressive.
Basically individuals should behave appropriately for their physical strength and their rank in the social hierarchy in order to avoid the wasteful conflicts. Our findings suggest that the vMHb-IPN ACh innervation is related to the evaluation of the strength of the opponents to resume the appropriate position in the dominance-submission relationship among the group.