Mechanisms underlying anoxic coma and spreading depolarization in Locusta mirgatoria
Van Dusen, Rachel
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Spreading depolarization (SD) is neurological phenomenon that results in the depression of neural activity and is found in both vertebrate and invertebrate systems. SD is characterized as a propagating wave of neuronal and glial depolarization. In invertebrate models this leads to complete neuromuscular shutdown. SD has been investigated in mammalian models for decades, as it is associated with many human pathologies including stroke, migraine and traumatic brain injury, however its occurrence in insects has only recently been determined. In the African migratory locust, L. migratoria, SD is associated with entry into a reversible stress-induced coma. Although there are many physiological differences in CNS properties between mammals and insects, the characteristics of SD remain consistent. For my thesis I used pharmacological and electrophysiological approaches to investigate the occurrence of SD in L. migratoria in response to anoxia. I characterized the variation in anoxic coma induction and recovery using three methods of anoxia, CO2 and N2 gas, and water immersion. These results showed that water immersion had increased coma induction and recovery times, whereas CO2 lead to shorter induction times and intermediate recovery times. I conclude that water immersion and N2 gas are the most useful methods of anoxic coma induction for future investigations. Additionally, I investigated the role of adenosine and adenosine receptor manipulation on coma recovery. Mammalian research shows that adenosine contributes to delayed synaptic recovery following SD. My results show that adenosine does delay recovery, however caffeine, as an adenosine receptor antagonist, decreased recovery times in whole animals and increased recovery times in semi-intact preparations. I investigated the potential pathways of adenosine receptor activation, exploring both cAMP and ATP-sensitive K+ (KATP) channel activation and inhibition. These results show that cAMP activation and KATP inhibition increased time to recover. Given these results, I discuss the similarity with mammalian findings and consider how this information contributes to a better understanding of the underlying mechanisms of SD.