Basal forebrain projections to the lateral habenula modulate aggression reward.
Basal forebrain projections to the lateral habenula modulate aggression reward.
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DOI：
10.1038/nature18601
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发表时间：
2016-06-30
期刊：
影响因子：
64.8
通讯作者：
Russo SJ
中科院分区：
文献类型：
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作者：
Golden SA;Heshmati M;Flanigan M;Christoffel DJ;Guise K;Pfau ML;Aleyasin H;Menard C;Zhang H;Hodes GE;Bregman D;Khibnik L;Tai J;Rebusi N;Krawitz B;Chaudhury D;Walsh JJ;Han MH;Shapiro ML;Russo SJ
适应不良的攻击性行为与许多神经精神疾病有关，被认为部分是由于大脑奖励系统对攻击性或暴力社会刺激的不适当激活。下丘脑腹内侧核团、杏仁核和边缘回路被认为编码攻击行为的起始，然而，直接调节攻击行为动机成分的神经机制却知之甚少。为了解决这一问题，我们建立了一个小鼠模型，以测量与一个较小的下属入侵者作为条件性位置偏好（CPP）的发展加强侵略性的雄性间的社会互动的效价。攻击者（AGG）发展了CPP，而非攻击者（NON）发展了条件性位置厌恶（CPA），入侵者配对的背景。此外，我们确定了从基底前脑（BF）到外侧缰（lHb）的功能性GABA能投射，其双向控制攻击性相互作用的效价。用盐视紫红质（NpHR 3.0）对AGG的GABA能BF-1Hb末端的回路特异性沉默增加了1Hb神经元的放电并消除了对入侵者配对背景的CPP。用通道视紫红质（ChR 2）激活NON的GABA能BF-1Hb末端减少1Hb神经元放电并促进对入侵者配对背景的CPP。最后，我们表明，改变抑制性传输在BF-1Hb终端不控制攻击行为的启动。这些结果表明，BF-1Hb回路在调节雄性间攻击行为的效价方面发挥着关键作用，并为调节攻击奖励处理的神经回路提供了新的机制见解。
Maladaptive aggressive behavior is associated with a number of neuropsychiatric disorders and is thought to partly result from 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 behavior. To address this, 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 (AGG) develop a CPP, while non-aggressors (NON) develop a conditioned place aversion (CPA), to the intruder-paired context. Further, 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 AGG with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of NON with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Lastly, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behavior. These results demonstrate that the BF-lHb circuit plays a critical role in regulating the valence of inter-male aggressive behavior and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.