Abstract
BackgroundAggression 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.ResultsSubstantial 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.ConclusionsThus, 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.
Highlights
Aggression is a near-universal behaviour with substantial influence on and implications for human and animal social systems
In non-human animals, aggression typically occurs in the context of competition for limited resources, including food, mates and nesting sites, where it is important in the establishment of territories and dominance hierarchies
When we compared these results with those for day 1 (Table 1), we found that in the hypothalamus of males (Fig. 6Bi), 88% of the genes overexpressed in dominants on day 1 were overexpressed on day 5: only the overexpressions of avpl and oxtl were specific to dominants in day 1, 11 genes were specific to dominant males on day 5
Summary
Aggression is a near-universal behaviour with substantial influence on and implications for human and animal social systems. In non-human animals, aggression typically occurs in the context of competition for limited resources, including food, mates and nesting sites, where it is important in the establishment of territories and dominance hierarchies In this respect, aggression is viewed as an adaptation that can have key effects on the lifelong success of individuals and that conveys evolutionary fitness [2]. One factor likely contributing to the limited knowledge on the control of aggression is that studies in this area have generally focused on linking specific neurotransmitters/neuroendocrine factors from individual pathways with the expression of aggressive behaviours. This approach does not build an understanding of the combination of factors and their interactions that form the biological determinants of this behaviour. This work has largely focused on a few select laboratory models (Drosophila and mouse [13,14,15,16,17,18]), has included the chicken [19] and honey bee [7]
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