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Tonic signaling from O2 sensors sets neural circuit activity and behavioral state

Abstract

Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that Caenorhabditis elegans O2-sensing neurons are tonic receptors that continuously signal ambient [O2] to set the animal's behavioral state. Sustained signaling relied on a Ca2+ relay involving L-type voltage-gated Ca2+ channels, the ryanodine and the inositol-1,4,5-trisphosphate receptors. Tonic activity evoked continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O2]. Sustained O2 receptor signaling was propagated to downstream neural circuits, including the hub interneuron RMG. O2 receptors evoked similar locomotory states at particular O2 concentrations, regardless of previous d[O2]/dt. However, a phasic component of the URX receptors' response to high d[O2]/dt, as well as tonic-to-phasic transformations in downstream interneurons, enabled transient reorientation movements shaped by d[O2]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change.

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Figure 1: High and low ambient O2 evoke different enduring behavioral states.
Figure 2: The AQR, PQR and URX O2 sensors are tonic receptors.
Figure 3: Light control of O2 receptor activity using halorhodopsin and channelrhodopsin.
Figure 4: Neuropeptide release from O2-sensors promotes the O2-evoked switch in behavioral state.
Figure 5: Tonic activation of O2 sensors is propagated to downstream interneurons, which are required for persistent behavioral change.
Figure 6: Anterior O2 sensors direct reversals, whereas posterior sensors direct forward movement.
Figure 7: Behavioral and neuronal responses to different d[O2]/dt.
Figure 8: The AVA interneurons display phasic responses to changes in O2.

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Acknowledgements

We thank the Caenorhabditis Genetics Center and the C. elegans Knockout Consortium for strains, members of the Schafer and de Bono laboratories for comments and insights in the course of this work and P. Dear for assistance with microfabrication. K.E.B. acknowledges support by European Union Marie Curie Actions, EMBO, the Swiss National Science Foundation and German Academic Exchange Service (DAAD). P.L. acknowledges support by EMBO and the Wiener-Anspach Foundation. Supported by Advanced European Research Council grant 269058-ACMO.

Author information

Authors and Affiliations

Authors

Contributions

K.E.B. and P.L. did Ca2+ imaging, behavioral assays, laser ablation, peptide assay and optogenetic experiments; H.L.S. helped with behavioral assays; P.L. and Z.S. developed the setup for Ca2+ imaging in freely moving worms; O.F., M.T. and B.H. designed and built the programmable array microscope; O.F., P.L. and K.E.B. conducted PAM experiments; R.J.M. and Z.S. wrote software; and K.E.B., P.L. and M.d.B. designed experiments, interpreted results and wrote the paper.

Corresponding author

Correspondence to Mario de Bono.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–10, Supplementary Strain List (PDF 9397 kb)

Supplementary Video 1

Halorhodopsin activation causes slowing in npr-1 lite1; pgcy-32::NpHR-mCherry animals kept at 21% O2. Movie is speeded up 18x. (MOV 2549 kb)

Supplementary Video 2

Channelrhodopsin activation causes speeding in npr-1 lite1; pgcy-32::ChR2-mCitrine animals kept at 11% O2. Movie is speeded up 18x. (MOV 2432 kb)

Supplementary Video 3

Selective channelrhodopsin activation of URX using the programmable array microscope elicits reversal behavior in npr-1 lite1; pgcy-32::ChR2-EYFP animals kept at 7% O2. Movie is in real time. (MOV 3441 kb)

Supplementary Video 4

Selective channelrhodopsin activation of PQR using the programmable array microscope elicits accelerated forward movement in npr-1 lite1; pgcy-32::ChR2-EYFP animals kept at 7% O2. Movie is in real time. (MOV 2899 kb)

Supplementary Video 5

A puff of 21% O2 directed at the head elicits reversal behavior in npr-1 animals kept at 7% O2. Movie is in real time. (MOV 815 kb)

Supplementary Video 6

A puff of 21% O2 directed at the tail elicits forward acceleration in npr-1 animals kept at 7% O2. Movie is in real time. (MOV 1795 kb)

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Busch, K., Laurent, P., Soltesz, Z. et al. Tonic signaling from O2 sensors sets neural circuit activity and behavioral state. Nat Neurosci 15, 581–591 (2012). https://doi.org/10.1038/nn.3061

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