Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice.,Nature Neuroscience

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Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2020-04-13 , DOI: 10.1038/s41593-020-0617-7
Meghan E Flanigan _{1,

2} , Hossein Aleyasin _{1,

2} , Long Li _{1,

2} , C Joseph Burnett _{1,

2} , Kenny L Chan _{1,

2} , Katherine B LeClair _{1,

2} , Elizabeth K Lucas _{1,

2,

3} , Bridget Matikainen-Ankney _{1,

2} , Romain Durand-de Cuttoli _{1,

2} , Aki Takahashi _{1,

2,

4} , Caroline Menard _{1,

2,

5} , Madeline L Pfau _{1,

2} , Sam A Golden ₆ , Sylvain Bouchard _{1,

2} , Erin S Calipari _{1,

2,

7} , Eric J Nestler _{1,

2} , Ralph J DiLeone ₈ , Akihiro Yamanaka ₉ , George W Huntley _{1,

2} , Roger L Clem _{1,

2} , Scott J Russo _{1,

2}

Affiliation

Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have various negative effects on patients, their families and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, domination of subordinate social targets is reinforcing. In this study, we showed that, in male mice, orexin neurons in the lateral hypothalamus activated a small population of glutamic acid decarboxylase 2 (GAD2)-expressing neurons in the lateral habenula (LHb) via orexin receptor 2 (OxR2) and that activation of these GAD2 neurons promoted male-male aggression and conditioned place preference for aggression-paired contexts. Moreover, LHb GAD2 neurons were inhibitory within the LHb and dampened the activity of the LHb as a whole. These results suggest that the orexin system is important for the regulation of inter-male aggressive behavior and provide the first functional evidence of a local inhibitory circuit within the LHb.

中文翻译：

GABA 能外侧缰核神经元中的食欲素信号传导调节雄性小鼠的攻击行为。

攻击性加剧是多种神经精神疾病的特征，可能对患者、其家人和公众产生各种负面影响。最近对人类和动物的研究表明，大脑奖励回路与攻击行为有关，并表明，在攻击性个体的子集中，对从属社会目标的支配正在加强。在这项研究中，我们发现，在雄性小鼠中，下丘脑外侧的食欲素神经元通过食欲素受体 2 (OxR2) 激活外侧缰核 (LHb) 中一小群表达谷氨酸脱羧酶 2 (GAD2) 的神经元，并且该激活这些 GAD2 神经元促进了男性之间的攻击行为，并对攻击配对环境产生了条件性位置偏好。此外，LHb GAD2 神经元在 LHb 内具有抑制作用，并抑制了 LHb 的整体活性。这些结果表明，食欲素系统对于调节雄性间的攻击行为很重要，并为 LHb 内的局部抑制回路提供了第一个功能证据。

更新日期：2020-04-13

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