Owing to the importance of acetylcholine
as a neurotransmitter,
many insecticides target the cholinergic system. Across phyla, cholinergic
signaling is essential for many neuro-developmental processes including
axonal pathfinding and synaptogenesis. Consequently, early-life exposure
to such insecticides can disturb these processes, resulting in an
impaired nervous system. One test frequently used to assess developmental
neurotoxicity is the zebrafish light–dark transition test,
which measures larval locomotion as a response to light changes. However,
it is only poorly understood which structural alterations cause insecticide-induced
locomotion defects and how persistent these alterations are. Therefore,
this study aimed to link locomotion defects with effects on neuromuscular
structures, including motorneurons, synapses, and muscles, and to
investigate the longevity of the effects. The cholinergic insecticides
diazinon and dimethoate (organophosphates), methomyl and pirimicarb
(carbamates), and imidacloprid and thiacloprid (neonicotinoids) were
used to induce hypoactivity. Our analyses revealed that some insecticides
did not alter any of the structures assessed, while others affected
axon branching (methomyl, imidacloprid) or muscle integrity (methomyl,
thiacloprid). The majority of effects, even structural, were reversible
within 24 to 72 h. Overall, we find that both neurodevelopmental and
non-neurodevelopmental effects of different longevity can account
for the reduced locomotion. These findings provide unprecedented insights
into the underpinnings of insecticide-induced hypoactivity.