Behavioral Responses to Hypoxia in Drosophila Larvae Are Mediated by Atypical Soluble Guanylyl Cyclases

Abstract

The three Drosophila atypical soluble guanylyl cyclases, Gyc-89Da, Gyc-89Db, and Gyc-88E, have been proposed to act as oxygen detectors mediating behavioral responses to hypoxia. Drosophila larvae mutant in any of these subunits were defective in their hypoxia escape response-a rapid cessation of feeding and withdrawal from their food. This response required cGMP and the cyclic nucleotide-gated ion channel, cng, but did not appear to be dependent on either of the cGMP-dependent protein kinases, dg1 and dg2. Specific activation of the Gyc-89Da neurons using channel rhodopsin showed that activation of these neurons was sufficient to trigger the escape behavior. The hypoxia escape response was restored by reintroducing either Gyc-89Da or Gyc-89Db into either Gyc-89Da or Gyc-89Db neurons in either mutation. This suggests that neurons that co-express both Gyc-89Da and Gyc-89Db subunits are primarily responsible for activating this behavior. These include sensory neurons that innervate the terminal sensory cones. Although the roles of Gyc-89Da and Gyc-89Db in the hypoxia escape behavior appeared to be identical, we also showed that changes in larval crawling behavior in response to either hypoxia or hyperoxia differed in their requirements for these two atypical sGCs, with responses to 15% oxygen requiring Gyc-89Da and responses to 19 and 25% requiring Gyc-89Db. For this behavior, the identity of the neurons appeared to be critical in determining the ability to respond appropriately.

Candidate ionotropic taste receptors in the Drosophila larva

“…It will be interesting to determine whether mutation of IR56a affects motor behavior. Likewise, the IR94d-GAL4 expression pattern resembles the expression pattern of oxygen-sensing cells that function in an escape response elicited by hypoxia (9).…”

“…5F). These neurons may have a chemosensory role in sensing local gas concentrations and in mediating an escape behavior that is triggered by hypoxia or hyperoxia (9,29); more detailed analysis will be required to determine their functional identity. Labeling was occasionally observed in the body wall of other abdominal segments.…”

“…Another organ, the dorsal pharyngeal organ (DPO), contains five neurons (3,5,8). A variety of other neurons in the body wall of the thorax and abdomen, and at the posterior tip of the larva, are also likely to be chemosensory (9)(10)(11).…”

Sleep- and wake-dependent changes in neuronal activity and reactivity demonstrated in fly neurons using in vivo calcium imaging

“…3C). The overall weaker response to oxygen relative to vinegar is expected because prior studies have shown that there are no oxygen-specific sensors in the antennal lobe and the response to oxygen results from either the airflow itself (27) or a decrease in carbon dioxide concentration (28)(29)(30). Finally, we also measured the response to oxygen and vinegar using a time series optimized for rapid imaging of a single plane spanning the cell body region and the calyx (see Materials and Methods for details).…”

Neuronal Inputs and Outputs of Aging and Longevity

“…Some examples are the mechanisms through which animals perceive oxygen levels within their environment. For example, environmental oxygen is sensed by specific soluble guanylyl cyclases (sGCs) in specific sensory neurons in C. elegans and Drosophila (Cheung et al, 2005;Chang et al, 2006;Rogers et al, 2006;Vermehren-Schmaedick et al, 2010). These sGCs regulate the aerotactic behaviors of the animals: C. elegans prefers 7-11% ambient oxygen and is repelled by hypoxic (<5% O 2 ) and hyperoxic (>14% O 2 ) environments (Cheung et al, 2005;Chang et al, 2006;Rogers et al, 2006); whereas Drosophila larvae prefer a more restricted range of O 2 concentration (∼21%) (VermehrenSchmaedick et al, 2010).…”