The Response to High CO2 Levels Requires the Neuropeptide Secretion Component HID-1 to Promote Pumping Inhibition

Abstract

Carbon dioxide (CO2) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO2 levels remain largely unknown. Here we report that acute CO2 exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO2 avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO2 levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO2 avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO2 levels on animals at the organism-wide level.

Control of Neuropeptide Expression by Parallel Activity-dependent Pathways in Caenorhabditis elegans

“…The C. elegans nervous system consists of 302 neurons, some of which function in non-overlapping circuits to regulate distinct behaviors. The BAG neurons for example are major regulators of acute CO 2 avoidance behavior 5 6 , the regulation of pharyngeal pumping rate when animals are exposed to high levels of CO 2 20 , and the control of egg laying 18 . The BAG neurons also act in conjunction with the URX neurons to coordinate behavioral responses to changes in O 2 gradients.…”

Optical silencing of body wall muscles induces pumping inhibition in Caenorhabditis elegans

“…Previous studies reported the involvement of UNC-31 in pumping inhibition caused by different types of stimuli [ 19 ][ 41 ][ 42 ]. We found that the pumping inhibition by green light illumination occurs even when I1 neurons, the sole connectors between the extra- and intra-pharyngeal nervous systems, were ablated.…”

Pharyngeal pumping inhibition and avoidance by acute exposure to high CO2levels are both regulated by the BAG neurons via different molecular pathways

“…However, all the CO 2 avoidance mutants that we tested showed a similar inhibition of the pumping in response to an acute high CO 2 exposure. 19 The mutants that we tested included mutants in chemo sensation (tax-4), nutritional state of the worm (daf-2), ciliated neuron development (osm-3, che-10) and CO 2 neuron specification (gcy-9,ets-5). To identify new components that mediate the response of the pharynx to high CO 2 , we performed a forward genetics screen after EMS mutagenesis.…”

“…23,25 By tissue specifically expressing HID-1 in a hid-1 null background, either in the gut (under a ges-1 promoter) or in the nervous system (under a rab-3 promoter), we demonstrated that hid-1 is only needed in the nervous system to mediate pumping inhibition. 19 We next searched for the neuronal subtype in which hid-1 mediates the effect of CO 2 on the pharynx. We used the nlp-3 promoter, which is expressed in neurons that secrete DCVs, to drive the expression of hid-1.…”

“…We discuss here our recent study of a previously uncharacterized behavioral response of C. elegans to elevated CO 2 , and a new component that is involved in C. elegans CO 2 signaling. 19 …”