Temperature sensitivity of spreading depolarization in the CNS of Drosophila melanogaster

During exposure to extreme stress, the central nervous system (CNS) of mammals and insects fails through a phenomenon known as spreading depolarization (SD). SD is characterized by an abrupt disruption of ion gradients across neural and glial membranes that spreads through the CNS, silencing neural activity. In humans, SD is associated with neuropathological conditions like migraine and stroke, while it coincides with critical thermal limits for activity in insects. In the latter, SD is conveniently monitored by recording the transperineurial potential (TPP), which we used to explore the plasticity and temperature dependence of SD thresholds and electrophysiological parameters in fruit flies (Drosophila melanogaster). Specifically, we characterized the effects of thermal acclimation on the characteristics of TPP changes during cold-induced SD, after which we induced SD with anoxia at different temperatures in both acclimation groups to examine the interactive effects of temperature and acclimation status. Lastly, we investigated how these affect the rate of SD propagation across the fly CNS. Cold acclimation enhanced resistance to both cold and anoxic SD, and our TPP measurements revealed independent and interactive effects of temperature and acclimation on the TPP and SD propagation. This suggests that thermodynamic processes and physiological mechanisms interact to modulate the thermal threshold for activity through SD and its electrophysiological phenomenology. These findings are discussed in relation to conceptual models for SD and established mechanisms for variation in the thermal threshold for SD, and we emphasize that future comparative or cross-species studies or translations must account for thermodynamic effects to improve inferences based on electrophysiology.NEW & NOTEWORTHY Thermal acclimation induces variation in the temperatures leading to spreading depolarization at the critical thermal limits in invertebrates, but mechanistic inferences based on electrophysiology might be skewed by thermodynamic effects. Here, we quantify the thermal dependence of spreading depolarization parameters in fruit flies, use it to infer mechanisms, and provide perspectives for future comparative research. In addition, we propose Drosophila as a model system to understand this event in vertebrates, including humans.