Figure 7. Proposed sequence of E.muscae-induced summiting mechanisms in zombie flies.

(A) Events in the host brain leading to E. muscae-induced summiting. (1) E. muscae cells are present in the brain as soon as 48 hr prior to death (Elya et al., 2018). (2) By 24 hr prior to death, the fungus is present at a high density in the superior medial protocerebrum (SMP). This corresponds to the ‘infected (doomed)’ status of flies in Figure 6. (3) E. muscae alters the hemolymph (perhaps by secreting compounds, as depicted here) to trigger the onset of summiting behavior. (4) Hemolymph-borne factors alter the activity of the circadian network/DN1p and pars intercerebralis to corpora allata (PI-CA) neurons. (5) Juvenile hormone (JH) is released from the corpora allata (CA) following changes in PI-CA activity. (6) Increased JH levels drive an increase in locomotion. The dashed outline of the brain becomes more prominent between steps 1 and 3 to reflect an increase in blood-brain barrier (BBB) permeability over these timepoints. (B) Left: Timeline of events depicted in (A) overlaid on cartoon plot of average relative y position (above) and speed (below) for zombie flies. Summiting is indicated by a black star; death (time of the last movement) is indicated by a fly ‘skull.’ Right: Zombie flies summited on a wooden dowel.