School of Biosciences, University of Exeter, Hatherly Laboratories, Prince of Wales Road, Exeter, Devon EX4 4PS, UK.
BMC Genomics. 2010 Sep 16;11:498. doi: 10.1186/1471-2164-11-498.
Aggression is a near-universal behaviour with substantial influence on and implications for human and animal social systems. The neurophysiological basis of aggression is, however, poorly understood in all species and approaches adopted to study this complex behaviour have often been oversimplified. We applied targeted expression profiling on 40 genes, spanning eight neurological pathways and in four distinct regions of the brain, in combination with behavioural observations and pharmacological manipulations, to screen for regulatory pathways of aggression in the zebrafish (Danio rerio), an animal model in which social rank and aggressiveness tightly correlate.
Substantial differences occurred in gene expression profiles between dominant and subordinate males associated with phenotypic differences in aggressiveness and, for the chosen gene set, they occurred mainly in the hypothalamus and telencephalon. The patterns of differentially-expressed genes implied multifactorial control of aggression in zebrafish, including the hypothalamo-neurohypophysial-system, serotonin, somatostatin, dopamine, hypothalamo-pituitary-interrenal, hypothalamo-pituitary-gonadal and histamine pathways, and the latter is a novel finding outside mammals. Pharmacological manipulations of various nodes within the hypothalamo-neurohypophysial-system and serotonin pathways supported their functional involvement. We also observed differences in expression profiles in the brains of dominant versus subordinate females that suggested sex-conserved control of aggression. For example, in the HNS pathway, the gene encoding arginine vasotocin (AVT), previously believed specific to male behaviours, was amongst those genes most associated with aggression, and AVT inhibited dominant female aggression, as in males. However, sex-specific differences in the expression profiles also occurred, including differences in aggression-associated tryptophan hydroxylases and estrogen receptors.
Thus, through an integrated approach, combining gene expression profiling, behavioural analyses, and pharmacological manipulations, we identified candidate genes and pathways that appear to play significant roles in regulating aggression in fish. Many of these are novel for non-mammalian systems. We further present a validated system for advancing our understanding of the mechanistic underpinnings of complex behaviours using a fish model.
攻击行为是一种普遍存在的行为，对人类和动物的社会系统有着重大的影响和意义。然而，所有物种的攻击行为的神经生理学基础都知之甚少，用于研究这种复杂行为的方法往往过于简单化。我们应用靶向表达谱分析了 40 个基因，这些基因跨越了 8 个神经通路，分布在大脑的 4 个不同区域，同时结合行为观察和药理学操作，以筛选斑马鱼（Danio rerio）的攻击调节通路，斑马鱼是一种社会等级和攻击性紧密相关的动物模型。
与攻击性表型差异相关的优势雄性和从属雄性之间的基因表达谱存在显著差异，而且对于所选的基因集，这些差异主要发生在下丘脑和端脑。差异表达基因的模式暗示了斑马鱼攻击行为的多因素控制，包括下丘脑-神经垂体系统、血清素、生长抑素、多巴胺、下丘脑-垂体-肾上腺、下丘脑-垂体-性腺和组胺途径，而后者是哺乳动物以外的一个新发现。下丘脑-神经垂体系统和血清素途径的各种节点的药理学操作支持它们的功能参与。我们还观察到优势雌性和从属雌性大脑表达谱的差异，表明攻击行为的性别保守控制。例如，在 HNS 途径中，编码精氨酸加压素（AVT）的基因，以前被认为是雄性行为特异性的，是与攻击行为最相关的基因之一，AVT 抑制了优势雌性的攻击行为，就像在雄性中一样。然而，表达谱也存在性别特异性差异，包括与攻击相关的色氨酸羟化酶和雌激素受体的差异。
因此，通过结合基因表达谱分析、行为分析和药理学操作的综合方法，我们确定了一些候选基因和途径，这些基因和途径似乎在调节鱼类的攻击行为中起着重要作用。其中许多在非哺乳动物系统中是新颖的。我们进一步提出了一个经过验证的系统，用于利用鱼类模型来推进我们对复杂行为的机制基础的理解。
