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 C. elegans O2-sensing neurons are tonic receptors that continuously signal ambient [O2] to set the animal’s behavioral state. Sustained signalling relies on a Ca2+ relay involving L-type voltage-gated Ca2+ channels, the ryanodine and the IP3 receptors. Tonic activity evokes continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O2]. Sustained O2 receptor signalling is propagated to downstream neural circuits, including the hub interneuron RMG. O2 receptors evoke similar locomotory states at particular [O2], 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, enable transient reorientation movements shaped by d[O2]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

“…The URX neurons sense increasing oxygen concentrations directly and are required for behavioral responses to oxygen upshifts that include reversals, turning, and increased locomotor speed (31,41,42). Expressing unc-1(n494) in the RMG circuit with the flp-21 promoter shifted the oxygen-dependent locomotion speed and reversal rates of npr-1 animals toward those of N2 animals ( Fig.…”

“…Early in its laboratory cultivation, the N2 strain of C. elegans acquired a gain-of-function mutation in the neuropeptide receptor NPR-1 that reconciled it to high oxygen levels (27). The npr-1(gf) mutation suppresses aggregation and oxygen avoidance, remodels pheromone responses, decreases locomotion speed on food, and results in a selective advantage in laboratory growth (26,(28)(29)(30)(31)(32)(33). These behaviors are controlled by a hub neuron called RMG, which has gap junctions with sensory neurons that detect ambient oxygen, pheromones, and other environmental cues (28).…”

Modulation of sensory information processing by a neuroglobin in Caenorhabditis elegans

“…To address this question, we quantified behavioral responses to a range of O 2 stimuli, focusing on reversal in the direction of movement and changes in speed, both important features of O 2 -evoked behaviors (18,19). Avoidance of high O 2 levels is mediated principally by three sensory neurons, URX, PQR, and AQR, each of which expresses the GCY-35/36 O 2 receptor and GLB-5 (11)(12)(13)18). To selectively study how URX output alters behavior we studied gcy-35(ok769); glb-5(tm5440) mutants that expressed glb-5(Haw) and/or gcy-35 cDNA in URX but not AQR or PQR (Methods).…”

“…Animals expressing GCaMP6s or cGi500 were glued to agarose pads (2% in M9 buffer) using Dermabond tissue adhesive (Ethicon), with the nose and tail immersed in E. coli OP50 unless otherwise indicated. Glued worms were covered with a polydimethylsiloxane (PDMS) microfluidic chamber, as described previously (12), and imaged using a 40× C-Apochromat lens on an inverted microscope (Axiovert; Zeiss) equipped with a Dual View emission splitter (Photometrics) and a Cascade II 512 electron multiplying charge coupled device (EMCCD) camera (Photometrics). The filters used were as follows: GCaMP6s/mCherry, ex480/15 and 565/15 nm, di525/25 and 625/45 nm, em520/30 nm, em630/50 nm, and di565 nm; and YFP-CFP FRET, ex430/20 nm, di450 nm, em480/30 nm, em535/40 nm, and di505 nm.…”

“…C. elegans avoids both normoxia (21% O 2 ) and hypoxia (11). Avoidance of 21% O 2 enables the animal to escape the surface and is mediated by O 2 receptors, most importantly the glb-5-expressing URX, AQR, and PQR neurons (12). Like vertebrate neuroglobins, GLB-5 has the spectroscopic fingerprints of a hexa-coordinated heme iron and rapidly oxidizes to the ferric state in normoxia (9).…”