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基底前脑向外侧缰核的投射调节攻击行为奖赏。

Basal forebrain projections to the lateral habenula modulate aggression reward.

作者信息

Golden Sam A, Heshmati Mitra, Flanigan Meghan, Christoffel Daniel J, Guise Kevin, Pfau Madeline L, Aleyasin Hossein, Menard Caroline, Zhang Hongxing, Hodes Georgia E, Bregman Dana, Khibnik Lena, Tai Jonathan, Rebusi Nicole, Krawitz Brian, Chaudhury Dipesh, Walsh Jessica J, Han Ming-Hu, Shapiro Matt L, Russo Scott J

机构信息

Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Graduate Program in Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

出版信息

Nature. 2016 Jun 30;534(7609):688-92. doi: 10.1038/nature18601.

Abstract

Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.

摘要

适应不良的攻击性行为与多种神经精神疾病有关,部分原因被认为是大脑奖赏系统在面对攻击性或暴力社会刺激时的不适当激活。已知腹内侧下丘脑、扩展杏仁核和边缘回路中的核团编码攻击行为的启动;然而,对于直接调节攻击性行为动机成分的神经机制知之甚少。在这里,我们建立了一个小鼠模型,以较小的从属入侵者作为条件性位置偏好(CPP)发展的强化物,来测量雄性间攻击性行为的效价。攻击者会形成CPP,而非攻击者会对与入侵者配对的环境产生条件性位置厌恶。此外,我们确定了一条从基底前脑(BF)到外侧缰核(lHb)的功能性γ-氨基丁酸能投射通路,该通路双向控制攻击性行为的效价。用嗜盐视紫红质(NpHR3.0)对攻击者的γ-氨基丁酸能BF-lHb终末进行回路特异性沉默,会增加lHb神经元的放电,并消除对与入侵者配对环境的CPP。用通道视紫红质(ChR2)激活非攻击者的γ-氨基丁酸能BF-lHb终末,会减少lHb神经元的放电,并促进对与入侵者配对环境的CPP。最后,我们表明改变BF-lHb终末的抑制性传递并不能控制攻击行为的启动。这些结果表明,BF-lHb回路在调节雄性间攻击性行为的效价方面具有关键作用,并为调节攻击奖赏处理的神经回路提供了新的机制性见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9bd/4930107/27c2670bd31d/nihms787738f5.jpg

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