Alterations of physiological regulatory networks and neuroendocrinological pathways in a parasitized vertebrate host expressing modified behaviour

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Our research program aims to understand the proximate pathways implicated in the modification of the behaviour of a vertebrate host (the threespine stickleback, Gasterosteus aculeatus) when parasitized by an internal tapeworm (Schistocephalus solidus). Sticklebacks act as an intermediate host in this parasite's complex life cycle. Parasitized fish show profoundly changed behaviour: they lose their response to predators, swim closer to the surface, feed at a higher rate under predation risk, and do not school with conspecifics. One of the crucial characteristics of this system is that the parasite grows far from the brain, within the body cavity of its host. The parasite goes through two developmental phases in the fish and these are paralleled by distinct behavioural and physiological phenotypes in the host: a non-infective phase in which the parasite grows to reach up to 90% of the host mass, and an infective stage in which the parasite is ready to move to its final bird host to reproduce. Infected fish show modified behaviour only during the second, infective phase. However, while biologists have fairly well mapped out the changes that occur at the organismal level in the host and when they happen, in comparison we know much less about what changes in the host at the molecular level. Understanding this would help us decipher the causes of the behavioural modifications observed in the host and ultimately to study the evolution of this parasite-host interaction. Based on the behavioural changes observed in the host, we can make predictions about which pathways may be affected. First, variation between individuals and between populations in the behavioural response to predators and in schooling opportunities in healthy sticklebacks has been shown to be associated with the stress response and brain monoamines. Second, daily vertical migrations are often found in fish and are associated with circadian rhythms. Third, it has been proposed that the secreted and excreted products from the parasite (the secretome) are sufficient to activate the immune system in its fish host. However, if and how these physiological regulatory systems are modified in infected fish, whether manipulating them could recreate the behaviour observed in a parasitized host, and if the secretome could alter host behaviour is unknown. We will characterise behaviours and physiological regulatory networks in hosts infected with worms at the non-infective and infective stage, and exposed to the secretome of Schistocephalus. We will measure acute physiological stress response, circadian rhythms and gene expression in the brain (RNA-seq) in specific brain regions. We will test the functional implications of the differences we will find using pharmacological manipulations. Our work will contribute to shed new light on this parasite-host system and on interactions between closely associated species in general.