Mitochondrial ROS as a regulator of synaptic function

Exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a well-studied hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis. Outside of the context of disease, the potential role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied. Here, we investigated this potential role by combining electrophysiological recordings, confocal imaging, immunohistochemical staining, and optogenetics using a well-established protocol for induction and measurement of synaptic potentiation in drosophila neuromuscular preparations. We have previously found that optogenetic induction of ROS emission from presynaptic mitochondria expressing mito-killer red was accompanied by an increase in spontaneous mini junction potentials. The increase in electrical activity did not appear to be associated with major synaptic structure alterations such as the formation of presynaptic filopodia or the growth of ghost boutons. However, in existing boutons, we observed an increase in active zone markers such as nc82/Brp. We have not detected Wnt1/Wg release from synaptic boutons suggesting the involvement of other signaling pathways that underlie observed changes in electrophysiological activity mediated by ROS emission. Future studies will further inquire the role of mitochondrial ROS in synaptic potentiation, as well as the potential signaling targets of mitochondrial ROS in the presynaptic structure.