Decoding a neural circuit controlling global animal state in C. elegans

Laurent, Patrick; Soltész, Zoltán; Nelson, Geoffrey M.; Chen, Changchun; Arellano‐Carbajal, Fausto; Levy, Emmanuel D.; Bono, Mario de

doi:10.7554/elife.04241

Cited by 75 publications

(122 citation statements)

References 91 publications

(158 reference statements)

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“…NPR-1 is a G proteincoupled receptor thought to be coupled to the Gi/o pathway, but its ultimate molecular target is not known (30,48). It is possible that NPR-1 regulates UNC-9-containing gap junctions directly, but it might also silence the RMG circuit by affecting excitability, synaptic transmission, or neuropeptide signaling (28,33,34,49).…”

Section: Discussionmentioning

confidence: 99%

“…3E). Although more detailed analysis may yield differences in URX calcium responses, these results suggest that oxygen-sensitive behavior might be regulated by npr-1 and gap junctions at a step downstream of or parallel to the initial URX calcium response (33).…”

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confidence: 93%

“…Alternative models for RMG signaling are possible, as all neurons in the circuit also have chemical synapses, and npr-1 also affects gene expression and neuropeptide signaling (32)(33)(34). Here we identify the unc-9 innexin gene as an essential component of the RMG circuit.…”

mentioning

confidence: 98%

“…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).…”

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confidence: 99%

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

Jang

Levy

Flavell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9-based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.innexin | neural circuits | electrical synapses | stomatin | sensory behavior

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Section: Discussionmentioning

confidence: 99%

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confidence: 93%

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confidence: 98%

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confidence: 99%

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

Jang

Levy

Flavell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…One important output for the URX O 2 sensors is the RMG interneurons, which are connected to URX by both synapses and gap junctions (21)(22)(23) ( Fig. S6).…”

Section: Resultsmentioning

confidence: 99%

Modulation of sensory information processing by a neuroglobin in Caenorhabditis elegans

Oda

Toyoshima

Bono

2017

Proc. Natl. Acad. Sci. U.S.A.

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T he response properties of sensory neurons can be characterized by tuning curves that relate stimulus parameters to the evoked response (1, 2). Some sensory neurons show dynamic ranges that span several orders of stimulus magnitude (e.g., odor concentration), whereas others show remarkably narrow tuning curves. For example, glomus cells of the carotid body show oxygenevoked responses that are tuned to a twofold to threefold change in O 2 levels at the physiologically appropriate O 2 concentration range (3, 4). How such sharp tuning is achieved is poorly understood.Neuroglobins are members of the globin family of hemebinding proteins expressed mainly in neurons (5). They have been described throughout metazoa, from cnidarians to man (6). Their physiological functions are unclear. They have been proposed to metabolize reactive oxygen species (ROS), signal redox state, store O 2 , control apoptosis, and negatively regulate Gi/o signaling (7). The genome of Caenorhabditis elegans encodes an unusually large family of globins, and many are expressed in neurons (8). One of these, GLOBIN-5 (GLB-5), is expressed in the oxygen sensing neurons URX, AQR, PQR, and BAG, where it accumulates at dendritic endings (9, 10). 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). The glb-5 gene is defective in the domesticated reference strain of C. elegans, N2 (Bristol), but natural isolates encode a functional allele, glb-5(Haw) (9, 10) (Haw refers to Hawaii, the geographical origin of the natural isolate in which this allele was first described). Behavioral and Ca 2+ imaging studies suggest that functional GLB-5 alters the properties of the O 2 receptors and C. elegans' O 2 responses (9, 10). However, how GLB-5 alters the representation of environmental information in these neurons leading to behavioral change is unknown.The URX O 2 receptors exhibit phasic-tonic signaling properties and, in response to changes in O 2 concentration, evoke both transient behavioral responses that are coupled to the rate of change of O 2 , dO 2 /dt, and more persistent behavioral responses coupled to O 2 levels (8, 13). The transient responses are reversals and turns that allow C. elegans to navigate O 2 gradients. The sustained responses involve persistent changes in the rate of movement that enable feeding animals to escape 21% O 2 or to accumulate in preferred lower O 2 environments. Besides GLB-5, the URX neurons express another putative molecular O 2 sensor, a soluble guanylate cyclase composed of GCY-35 and GCY-36 (guanylate cyclase) subunits (11,13,14). These soluble guanylate cyclases have a heme-nitric oxide/oxygen (H-NOX) binding domain that appears to stimulate cGMP production upon binding molecular O 2 (10, ...

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Genes and Behaviour

Weitekamp

Keller

2019

Genes and Behaviour

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Decoding a neural circuit controlling global animal state in C. elegans

Cited by 75 publications

References 91 publications

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

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

Modulation of sensory information processing by a neuroglobin in Caenorhabditis elegans

Genes and Behaviour

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