Social experience and sex-dependent regulation of aggression in the lateral septum by extrasynaptic δGABAA receptors
Social experience and sex-dependent regulation of aggression in the lateral septum by extrasynaptic δGABAA receptors
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DOI：
10.1007/s00213-019-05368-z
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发表时间：
2019-11-06
影响因子：
3.4
通讯作者：
Albers, H. Elliott
中科院分区：
文献类型：
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作者：
Borland, Johnathan M.;Walton, James C.;Albers, H. Elliott
基本原理 了解介导支配地位和竞争性攻击的神经生物学机制对于了解各种精神疾病的发展和治疗至关重要。先前的研究表明，这些机制都存在性别差异，并且很大程度上受到社会经验的影响。在许多物种中，侧隔膜中的 GABA(A) 受体已被证明在雄性的攻击性中发挥着重要作用。然而，人们对这些 GABA(A) 受体在女性攻击性中的作用、社会经验对 GABA(A) 受体介导的攻击性的作用或不同 GABA(A) 亚型在调节攻击性中的作用知之甚少。因此，在下面的一组实验中，我们确定了社会经验在调节雄性和雌性叙利亚仓鼠 GABA(A) 受体诱导的攻击行为中的作用，特别关注介导这些作用的 GABA(A) 受体亚型。结果背外侧隔膜中 GABA(A) 受体的激活增加了雄性和雌性的攻击性。然而，社会住房显着降低了 GABA(A) 受体激活诱发男性攻击性的能力，但对女性则没有影响。在群养仓鼠中，主导组与从属组饲养的仓鼠中，GABA(A) 受体激活的影响没有观察到显着差异。最后，对潜在 GABA(A) 受体亚型特异性的检查表明，社会住房降低了背侧外侧隔中 δ 突触外与 γ(2) 突触亚基 GABA(A) 受体 mRNA 表达的比率，而背侧外侧隔中 δ 突触外 GABA(A) 受体的激活增加了攻击性，但不是 γ(2) 突触。结论 这些数据表明，社会经验可以对介导攻击性的神经元机制产生深远的影响，尤其是在男性中，并且 δ 突触外 GABA(A) 受体可能是以高水平攻击性为特征的疾病的重要治疗靶点。
Rationale Understanding the neurobiological mechanisms mediating dominance and competitive aggression is essential to understanding the development and treatment of various psychiatric disorders. Previous research suggests that these mechanisms are both sexually differentiated and influenced substantially by social experience. In numerous species, GABA(A) receptors in the lateral septum have been shown to play a significant role in aggression in males. However, very little is known about the role of these GABA(A) receptors in female aggression, the role of social experience on GABA(A) receptor-mediated aggression, or the roles of different GABA(A) subtypes in regulating aggression. Objectives Thus, in the following set of experiments, we determined the role of social experience in modulating GABA(A) receptor-induced aggression in both male and female Syrian hamsters, with a particular focus on the GABA(A) receptor subtype mediating these effects. Results Activation of GABA(A) receptors in the dorsal lateral septum increased aggression in both males and females. Social housing, however, significantly decreased the ability of GABA(A) receptor activation to induce aggression in males but not females. No significant differences were observed in the effects of GABA(A) receptor activation in dominant versus subordinate group-housed hamsters. Finally, examination of potential GABA(A) receptor subtype specificity revealed that social housing decreased the ratio of delta extrasynaptic to gamma(2) synaptic subunit GABA(A) receptor mRNA expression in the anterior dorsal lateral septum, while activation of delta extrasynaptic, but not gamma(2) synaptic, GABA(A) receptors in the dorsal lateral septum increased aggression. Conclusions These data suggest that social experience can have profound effects on the neuronal mechanisms mediating aggression, especially in males, and that delta extrasynaptic GABA(A) receptors may be an important therapeutic target in disorders characterized by high levels of aggression.