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bioRxiv · 10.1101/2022.12.01.518723

Neural mechanisms of parasite-induced summiting behavior in 'zombie' Drosophila

Elya, C.·Lavrentovich, D.·Lee, E.·Pasadyn, C.·Duval, J.·Basak, M.·Saykina, V.·de Bivort, B. L.
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Abstract

For at least two centuries, scientists have been enthralled by the "zombie" behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the recently established Entomophthora muscae-Drosophila melanogaster "zombie fly" system to reveal the molecular and cellular underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a new, high-throughput behavior assay to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), who are solely responsible for juvenile hormone (JH) synthesis and release. Summiting is a fleeting phenomenon, posing a challenge for physiological and biochemical experiments requiring tissue from summiting flies. We addressed this with a machine learning classifier to identify summiting animals in real time. PI-CA neurons and CA appear to be intact in summiting animals, despite E. muscae cells invading the host brain, particularly in the superior medial protocerebrum (SMP), the neuropil that contains DN1p axons and PI-CA dendrites. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the flys hemolymph, activating the neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.

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Elya, C., Lavrentovich, D., Lee, E., Pasadyn, C., Duval, J., Basak, M., Saykina, V., de Bivort, B. L.. 2022-12-01. Neural mechanisms of parasite-induced summiting behavior in 'zombie' Drosophila. https://doi.org/10.1101/2022.12.01.518723

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