2025-04-10 理化学研究所
<関連情報>
- https://www.riken.jp/press/2025/20250410_2/index.html
- https://www.cell.com/current-biology/fulltext/S0960-9822(25)00352-5
マウスにおける社会的優劣葛藤の結果を制御する手綱核-間脳下垂体-正中ラプスの経路 The habenula-interpeduncular nucleus-median raphe pathway regulates the outcome of social dominance conflicts in mice
Miho Matsumata∙ Kenzo Hirao∙ Takuma Kobayashi∙ … ∙ Deepa Kamath Kasaragod∙ Thomas J. McHugh∙ Hitoshi Okamoto
Current Biology Published:April 9, 2025
DOI:https://doi.org/10.1016/j.cub.2025.03.036
Graphical abstract
Highlights
- Inhibition of the cholinergic habenula-IPN pathway makes mice win in social conflict
- The disinhibition of 5-HT neurons in the median raphe (MnR) underlies this bias
- Conversely, the activation of this pathway makes mice prone to defeat
- Defeated mice can be rescued by chemogenetic activation of 5-HT neurons in the MnR
Summary
The habenula (Hb) to interpeduncular nucleus (IPN) projection is highly conserved across vertebrates and, in zebrafish, has been shown to regulate the decision between continuing to fight and surrender during social conflict. We have recently shown that, in loser zebrafish, habenular acetylcholine release acts on postsynaptic α7 nicotinic receptors to induce the expression of Ca2+-permeable AMPA receptors on the silent synapses of the IPN neurons that project to the median raphe (MnR). Leveraging this evolutionary conservation, we demonstrate that the disruption of cholinergic transmission from the Hb to the IPN biases mice toward winning social conflicts, whereas optogenetic activation has the opposite effect of biasing toward losing. Further circuit dissection revealed that the losing bias is likely to be mediated via inhibition of serotonin (5-hydroxytryptamine [5-HT]) neurons in the MnR by the IPN.
