Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6151-6. doi: 10.1073/pnas.1303446110. Epub 2013 Mar 25.
Monoamines, including dopamine (DA), have been linked to aggression in various species. However, the precise role or roles served by the amine in aggression have been difficult to define because dopaminergic systems influence many behaviors, and all can be altered by changing the function of dopaminergic neurons. In the fruit fly, with the powerful genetic tools available, small subsets of brain cells can be reliably manipulated, offering enormous advantages for exploration of how and where amine neurons fit into the circuits involved with aggression. By combining the GAL4/upstream activating sequence (UAS) binary system with the Flippase (FLP) recombination technique, we were able to restrict the numbers of targeted DA neurons down to a single-cell level. To explore the function of these individual dopaminergic neurons, we inactivated them with the tetanus toxin light chain, a genetically encoded inhibitor of neurotransmitter release, or activated them with dTrpA1, a temperature-sensitive cation channel. We found two sets of dopaminergic neurons that modulate aggression, one from the T1 cluster and another from the PPM3 cluster. Both activation and inactivation of these neurons resulted in an increase in aggression. We demonstrate that the presynaptic terminals of the identified T1 and PPM3 dopaminergic neurons project to different parts of the central complex, overlapping with the receptor fields of DD2R and DopR DA receptor subtypes, respectively. These data suggest that the two types of dopaminergic neurons may influence aggression through interactions in the central complex region of the brain involving two different DA receptor subtypes.
单胺类物质,包括多巴胺(DA),与各种物种的攻击性有关。然而,由于多巴胺能系统会影响许多行为,而且改变多巴胺能神经元的功能都会改变所有这些行为,因此,胺在攻击性中的作用或作用一直难以确定。在果蝇中,由于有强大的遗传工具可用,因此可以可靠地操纵小部分脑细胞,这为探索胺能神经元如何以及在何处适应与攻击性相关的电路提供了巨大的优势。通过将 GAL4/上游激活序列(UAS)二元系统与翻转酶(FLP)重组技术相结合,我们能够将靶向 DA 神经元的数量限制在单细胞水平。为了探索这些单个多巴胺能神经元的功能,我们用破伤风毒素轻链使它们失活,破伤风毒素轻链是一种遗传编码的神经递质释放抑制剂,或者用 dTrpA1 使它们激活,dTrpA1 是一种温度敏感的阳离子通道。我们发现了两组调节攻击性的多巴胺能神经元,一组来自 T1 簇,另一组来自 PPM3 簇。这些神经元的激活和失活都会导致攻击性增加。我们证明,鉴定出的 T1 和 PPM3 多巴胺能神经元的突触前末端投射到中央复合体的不同部位,分别与 DD2R 和 DopR DA 受体亚型的受体场重叠。这些数据表明,这两种类型的多巴胺能神经元可能通过涉及两种不同的 DA 受体亚型的大脑中央复合体区域的相互作用来影响攻击性。