Dual Excitatory and Inhibitory Serotonergic Inputs Modulate Egg Laying in<i>Caenorhabditis elegans</i>

Hapiak, Vera; Hobson, Robert J.; Hughes, Lindsay J.; Smith, Kendra Schank; Harris, Graham P.; Condon, Christina; Komuniecki, Patricia R.; Komuniecki, Richard

doi:10.1534/genetics.108.096891

Cited by 68 publications

(113 citation statements)

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“…GOA-1 is the C. elegans ortholog of the major neural G protein Ga o (Lochrie et al 1991) and is a member of the Ga i/o class of G proteins thought to be activated by SER-4 (Olde and McCombie 1997). Serotonin resistance of MOD-1, SER-4, and GOA-1 mutants has been noted previously (Ségalat et al 1995;Ranganathan et al 2000;Hapiak et al 2009) and suggests that serotonin acts directly on two different receptors to inhibit locomotion.…”

Section: Resultsmentioning

confidence: 98%

“…Many past studies of serotonin signaling in C. elegans have analyzed gene knockouts for worm homologs of serotonin-signaling proteins already known from studies in vertebrates. For example, mutants defective in enzymes required for serotonin biosynthesis and for serotonin receptor homologs have revealed a number of behaviors that depend on serotonin (Sze et al 2000;Carnell et al 2005;Dempsey et al 2005;Hobson et al 2006;Dernovici et al 2007;Hapiak et al 2009;Harris et al 2009). However, the greatest potential for C. elegans genetics to illuminate mechanisms of serotonin signaling likely lies in genetic screens to discover new serotonin-signaling proteins not previously known from vertebrate studies.…”

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Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

et al. 2012

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A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. DEPRESSION is hypothesized to involve dysfunction of the neurotransmitter serotonin (Cowen 2008). Understanding the molecular mechanism of serotonin signaling is complicated by the fact that the human brain expresses 14 types of serotonin receptors, one of which is a serotonin-gated ion channel, and the rest of which are G-protein-coupled receptors (Millan et al. 2008). An additional challenge to understanding serotonin signaling is the fact that serotonin can act locally at synapses where it is released or diffuse away and act at distant receptors. While classical neurotransmitters such as GABA and glutamate appear to function mainly locally at synapses, serotonin can diffuse several microns from its release sites at concentrations sufficient to activate its receptors (Bunin and Wightman 1998). Furthermore, serotonin receptors are often localized at nonsynaptic sites (Kia et al. 1996). These observations suggest that serotonin might act predominantly as an extrasynaptic signal to activate several receptor types on cells distant from its release sites and that the combined action of these several receptors somehow coordinates appropriate responses to serotonin. The details of how such action might occur remain unclear.Caenorhabditis elegans uses serotonin as a neurotransmitter (Horvitz et al. 1982;Chase and Koelle 2007) and provides a model system with the potential to make important contributions to the study of serotonin signaling. First, C. elegans allows the use of forward genetic screens to identify the proteins beyond serotonin receptors that mediate serotonin response. Second, the known...

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Section: Resultsmentioning

confidence: 98%

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Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

et al. 2012

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“…Their role appears to be modulatory because their absence reduces the response robustness, but not induction, of B-neuron-induced tail curling. In the hermaphrodite, serotonin and FMRF-amides have complex neuromodulatory effects on several worm motor behaviors, including egg laying and locomotion (Nelson et al, 1998;Rogers et al, 2006;Hapiak et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

The Robustness ofCaenorhabditis elegansMale Mating Behavior Depends on the Distributed Properties of Ray Sensory Neurons and Their Output through Core and Male-Specific Targets

Koo

Bian²,

Sherlekar³

et al. 2011

J. Neurosci.

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Many evolutionarily significant behaviors, such as mating, involve dynamic interactions with animate targets. This raises the question of what features of neural circuit design are essential to support these complex types of behavior. The Caenorhabditis elegans male uses 18 ray sensilla of the tail to coordinate mate apposition behavior, which facilitates a systematic search of the hermaphrodite surface for the vulva. Precisely how ray neuron types, A and B, robustly endow the male with a high degree of spatial and temporal precision is unknown. We show that the appositional postures that drive the search trajectory reflect the complex interplay of ray neuron type-induced motor outputs. Cell-type-specific ablations reveal that the A-neurons are required for all appositional postures. Their activity is instructive because the A-neurons can induce scanning-and turning-like appositional postures when artificially activated with channelrhodopsin (ChR2). B-neurons are essential only for initiation of the behavior in which they enhance male responsiveness to hermaphrodite contact. When artificially activated using ChR2, A-and B-neurons produce different tail ventral curl postures. However, when coactivated, A-neuron posture dominates, limiting B-neuron contributions to initiation or subsequent postures. Significantly, males lacking the majority of rays retain a high degree of postural control, indicating significant functional resilience in the system. Furthermore, eliminating a large number of male-specific ray neuron targets only partially attenuates tail posture control revealing that gender-common cells make an important contribution to the behavior. Thus, robustness may be a crucial feature of circuits underlying complex behaviors, such as mating, even in simple animals. IntroductionHow animals sense the relevant features of their environment and translate this information into appropriate motor responses is perhaps the overarching question in neuroscience. Ultimate and proximate mechanisms underlying mating success and the transmission of heritable information to the next generation is a central concern for evolutionary biology. The nematode worm Caenorhabditis elegans represents a valuable model system for exploring the molecular and cellular underpinnings of these two fundamental questions. Many studies of C. elegans behavior (for example, chemotaxis, thermotaxis, and mechanosensation) use hermaphrodites in simple behavioral assays (for review, see Bargmann, 2006;Goodman, 2006;Garrity et al., 2010). These behaviors are mediated by relatively few sensory receptor cells with limited in-built redundancy (Chalfie and Sulston, 1981;Bargmann and Horvitz, 1991;Biron et al., 2008). However, many evolutionarily significant behaviors involve dynamic interactions with animate targets. This raises the question of what features of neural circuit design are essential for supporting these more complex types of behavior. C. elegans male mating behavior consists of a carefully orchestrated sequence of sensorimotor transformati...

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“…MOD-1 is a novel 5-HT-gated chloride channel and is expressed in the AIA, AIB, AIY, AIZ and RID interneurons, as well as in a number of additional unidentified neurons in the head, ventral cord and tail 24,25 . MOD-1 has been suggested to function in regulating locomotion [24][25][26][27] and egg laying 28,29 . However, it is unclear whether MOD-1 is involved in feeding regulation.…”

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Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation

et al. 2012

Nat Commun

110

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Feeding behaviour is modulated by both environmental cues and internal physiological states. Appetite is commonly boosted by the pleasant smell (or appearance) of food and destroyed by a bad taste. In reality, animals sense multiple environmental cues at the same time and it is not clear how these sensory inputs are integrated and a decision is made to regulate feeding behaviour accordingly. Here we show that feeding behaviour in Caenorhabditis elegans can be either facilitated by attractive odours or suppressed by repellents. By identifying mutants that are defective for sensory-mediated feeding regulation, we dissected a central flip-flop circuit that integrates two contradictory sensory inputs and generates bistable hormone output to regulate feeding behaviour. As feeding regulation is fundamental to animal survival, we speculate that the basic organizational logic identified here in C. elegans is likely convergent throughout different phyla.

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Dual Excitatory and Inhibitory Serotonergic Inputs Modulate Egg Laying inCaenorhabditis elegans

Cited by 68 publications

References 52 publications

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion inCaenorhabditis elegans

The Robustness ofCaenorhabditis elegansMale Mating Behavior Depends on the Distributed Properties of Ray Sensory Neurons and Their Output through Core and Male-Specific Targets

Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation

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