Central nervous shutdown underlies acute cold tolerance in tropical and temperateDrosophilaspecies

Abstract

When cooled, insects first lose their ability to perform coordinated movements (CT) after which they enter chill coma (chill coma onset, CCO). Both these behaviours are popular measures of cold tolerance that correlate remarkably well with species distribution. To identify and understand the neuromuscular impairment that causes CT and CCO we used inter- and intraspecific model systems of species that have varying cold tolerance as a consequence of adaptation or cold acclimation. Our results demonstrate that CT and CCO correlate strongly with a spreading depolarization (SD) within the central nervous system (CNS). We show that this SD is associated with a rapid increase in extracellular [K] within the CNS causing neuronal depolarization that silences the CNS. The CNS shutdown is likely to be caused by a mismatch between passive and active ion transport within the CNS and in a different set of experiments we examine inter- and intraspecific differences in sensitivity to SD events during anoxic exposure. These experiments show that cold adapted or acclimated flies are better able to maintain ionoregulatory balance when active transport is compromised within the CNS. Combined, we demonstrate that a key mechanism underlying chill coma entry of is CNS shutdown, and the ability to prevent this CNS shutdown is therefore an important component of acute cold tolerance, thermal adaptation and cold acclimation in insects.

Cold stress results in sustained locomotor and behavioral deficits in Drosophila melanogaster

“…Insect thermal tolerance is an important factor mediating population range and dynamics, possibility of invasion, and response to global climate change (Addo‐Bediako et al, ; J. L. Andersen et al, ; Bellard et al, ; Youngsteadt et al, ). As such, great efforts have been devoted to understanding the molecular, physiological, and evolutionary underpinnings of insect thermal tolerance (Andersen et al, ; Andersen et al, ; Findsen et al, ; Macmillan et al, ; Macmillan et al, ). However, there are still gaps in our understanding of the behavioral consequences of cold stress.…”

“…Cold exposure can lead to short-term disruptions in physiology, e.g., dysregulation of ion homeostasis , and long-term fitness consequences, e.g., reduced fecundity (Marshall & Sinclair, 2010;Rinehart et al, 2000). Disruption of membrane polarity and ion balance can cause a decline in neuromuscular cell survival and function (Andersen et al, 2017;Andersen et al, 2018;Findsen et al, 2016;Macmillan et al, 2014Macmillan et al, , 2015 assessing behavioral responses to cold stress using the RING assay.…”

“…L. Andersen et al, 2015;Bellard et al, 2013;Youngsteadt et al, 2017). As such, great efforts have been devoted to understanding the molecular, physiological, and evolutionary underpinnings of insect thermal tolerance (Andersen et al, 2017;Andersen et al, 2018;Findsen et al, 2016;Macmillan et al, 2014;Macmillan et al, 2015). However, there are still gaps in our understanding of the behavioral consequences of cold stress.…”

“…Cold stress affects multiple physiological processes simultaneously (Teets & Denlinger, ), and recent literature indicates that dysregulation of ion balance is a principle route of cold injury (Overgaard & Macmillan, ). Thus, tissues like nerves and muscles, which are highly dependent on ion homeostasis for proper functionality, are particularly sensitive to cold injury (Andersen, Folkersen, MacMillan, & Overgaard, ; Andersen, Jensen, Robertson, & Overgaard, ; Findsen, Overgaard, & Pedersem, ; Macmillan, Baatrup, Overgaard & Macmillan, ; Macmillan et al, ). However, the effects of cold stress on complex behaviors that depend on neuromuscular function have garnered relatively little attention.…”

Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

“…70,71 Indeed, multiple studies have shown beneficial properties of SD, including preconditioning, upregulation of growth factors, and neurogenesisis. [72][73][74][75][76][77] In addition, previous studies in insects [78][79][80][81] and rodents 72,73,82,83 suggest that SD may play a neuroprotective role during ischemia. 1,84 It is possible that this protection is enabled by a "neuronal silencing" mechanism associated with SD 85 wherein metabolism is quickly shut down, possibly to conserve residual energy and minimize production of reactive oxygen species, potentially leading to an improved survival and outcome in reversible processes.…”