Grant: Discovery Grants Program - Individual

Parasitic manipulators are parasites that actively alter host behaviour, leading to increased parasite success. Our lab will study how the parasitic wasp, Cotesia congregata, alters the brain and behaviour of its host, the caterpillar Manduca sexta. Parasitic manipulators alter host behaviour using methods that are unexplored by neurobiologists, providing the potential for novel discoveries. This proposal integrates behavioural, biochemical, physiological, and molecular studies.    The wasp needs a caterpillar to complete its life cycle. The female wasp injects both eggs and a domesticated virus (a polydnavirus, PDV) into the body of its host. The PDV transfers wasp genes into the brain of the caterpillar. Although the developing wasp larvae induce physiological changes in their host; caterpillar behaviour is normal until the wasp larvae exit through the caterpillar's body wall. As the wasps exit from the host, the caterpillar stops feeding and eventually starves to death. However, the caterpillar retains its defensive reflexes. The caterpillar becomes an anorexic bodyguard for the wasp cocoons, protecting them from arthropod predators. Without their bodyguard, the cocoons are usually eaten.    I hypothesize that the wasp turns it host into a bodyguard by exploiting an immune-neural connection. During an immune response, caterpillars show illness-induced anorexia that promotes their recovery. When the wasps exit the host, they create a massive immune response that activates immune-neural connections. At the same time, the PDV induces a burst of viral protein production in the caterpillar brain. I suggest that this burst induces neuroinflammation, amplifying the immune-neural signals.    To test this hypothesis, our lab will show that neuroinflammation occurs in caterpillar brains at wasp emergence using qPCR, metabolomics, and electron microscopy. Our lab will test whether we can rescue feeding behaviour by preventing neuroinflammatory damage in the brain. We will also test whether the increase in PDV gene expression at wasp emergence is necessary for inducing bodyguard behaviour and/or neuroinflammation. Finally, we will examine whether an immune challenge and/or the wasps suppress the feeding circuit of the caterpillar by altering the ratio of important neuromodulators.    The proposed research will significantly advance the field of parasitic manipulation by increasing our understanding of how parasites can reprogram neural circuits using immune-neural connections. This study will also set the stage for determining how activation of some genes can lead to a state of permanent neuroinflammation, a source of serious neuropathology. I predict that our study will show that the wasp uses many small neurophysiological nudges on its host, as opposed to strongly altering a single target. Such a result would suggest that studying gene ensembles, instead of single genes, will be important for understanding brain function.