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Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release.

Choi S, Taylor KP, Chatzigeorgiou M, Hu Z, Schafer WR, Kaplan JM - PLoS Genet. (2015)

Bottom Line: Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1.These sensory neurons accelerate locomotion via both neuropeptide and glutamate release.Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America; Biological and Biomedical Sciences program, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), and stretch sensing (DVA) neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states.

No MeSH data available.


Related in: MedlinePlus

GLR-2 AMPA receptors are required for the npr-1 lethargus defect.Locomotion behavior of single worms during the L4/A lethargus (A-E and H-J) and in adults (F, K) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, H), average motile fraction (B, D, and I), and average locomotion velocity (C, E, F, J and K) are plotted. (A-C) The npr-1 locomotion defect during L4/A lethargus was suppressed by mutations inactivating glr-2 AMPA receptors, and partially reinstated by transgenes expressing GLR-2 in AIA (gcy-28(d) promoter) and DVA (nlp-12 promoter) neurons, but not in Ventral Cord Interneurons (V.C.I., glr-1 promoter) in glr-2;npr-1 double mutants using the indicated promoters. (D-E) glr-1 mutations had no suppressing effect. (F) glr-2 mutations did not block the increased locomotion in npr-1 adults. (G) mEPSCs were recorded from body wall muscles of the adult worms for the indicated genotypes. Summary data are shown. (G) glr-2 mutations did not block the increased mEPSC rate in npr-1 adults. (H-K) Locomotion behavior during the L4/A lethargus (H-J) and in adults (K) of single worms whose DVA neuron is ablated by transgenic overexpression of CED-3 in DVA neuron (nlp-12 promoter) was analyzed in the indicated genotypes. Animals were analyzed by fluorescence microscopy after locomotion recordings to determine if DVA was ablated. The npr-1 locomotion defect during the L4/A lethargus, but not in adults, was partially suppressed in the transgenic animals in which DVA was ablated (-DVA). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (**, p <0.01; ***, p <0.001; ns, not significant).
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pgen.1005359.g005: GLR-2 AMPA receptors are required for the npr-1 lethargus defect.Locomotion behavior of single worms during the L4/A lethargus (A-E and H-J) and in adults (F, K) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, H), average motile fraction (B, D, and I), and average locomotion velocity (C, E, F, J and K) are plotted. (A-C) The npr-1 locomotion defect during L4/A lethargus was suppressed by mutations inactivating glr-2 AMPA receptors, and partially reinstated by transgenes expressing GLR-2 in AIA (gcy-28(d) promoter) and DVA (nlp-12 promoter) neurons, but not in Ventral Cord Interneurons (V.C.I., glr-1 promoter) in glr-2;npr-1 double mutants using the indicated promoters. (D-E) glr-1 mutations had no suppressing effect. (F) glr-2 mutations did not block the increased locomotion in npr-1 adults. (G) mEPSCs were recorded from body wall muscles of the adult worms for the indicated genotypes. Summary data are shown. (G) glr-2 mutations did not block the increased mEPSC rate in npr-1 adults. (H-K) Locomotion behavior during the L4/A lethargus (H-J) and in adults (K) of single worms whose DVA neuron is ablated by transgenic overexpression of CED-3 in DVA neuron (nlp-12 promoter) was analyzed in the indicated genotypes. Animals were analyzed by fluorescence microscopy after locomotion recordings to determine if DVA was ablated. The npr-1 locomotion defect during the L4/A lethargus, but not in adults, was partially suppressed in the transgenic animals in which DVA was ablated (-DVA). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (**, p <0.01; ***, p <0.001; ns, not significant).

Mentions: To determine if increased ASH activity is sufficient to arouse locomotion, we analyzed locomotion after artificially depolarizing ASH neurons. For this experiment, we utilized transgenic animals that express rat TRPV1 capsaicin receptors in ASH neurons [24]. In these animals, capsaicin treatment evokes ASH-mediated avoidance behaviors [24]. A 5-hour capsaicin treatment had little effect on L4/A motile fraction and locomotion velocity [11], whereas capsaicin treatment significantly accelerated adult locomotion and increased aldicarb sensitivity (Figs 4I–5J and S2G Fig). These effects were not observed in animals lacking TRPV1 expression in ASH neurons (Fig 4I and 4J). Thus, forced ASH depolarization was sufficient to arouse adult but not lethargus locomotion. Collectively, these results suggest that diminished and heightened ASH activity is associated with locomotion quiescence and arousal respectively; however, the magnitude of ASH’s arousing effects differ between lethargus and adult animals.


Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release.

Choi S, Taylor KP, Chatzigeorgiou M, Hu Z, Schafer WR, Kaplan JM - PLoS Genet. (2015)

GLR-2 AMPA receptors are required for the npr-1 lethargus defect.Locomotion behavior of single worms during the L4/A lethargus (A-E and H-J) and in adults (F, K) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, H), average motile fraction (B, D, and I), and average locomotion velocity (C, E, F, J and K) are plotted. (A-C) The npr-1 locomotion defect during L4/A lethargus was suppressed by mutations inactivating glr-2 AMPA receptors, and partially reinstated by transgenes expressing GLR-2 in AIA (gcy-28(d) promoter) and DVA (nlp-12 promoter) neurons, but not in Ventral Cord Interneurons (V.C.I., glr-1 promoter) in glr-2;npr-1 double mutants using the indicated promoters. (D-E) glr-1 mutations had no suppressing effect. (F) glr-2 mutations did not block the increased locomotion in npr-1 adults. (G) mEPSCs were recorded from body wall muscles of the adult worms for the indicated genotypes. Summary data are shown. (G) glr-2 mutations did not block the increased mEPSC rate in npr-1 adults. (H-K) Locomotion behavior during the L4/A lethargus (H-J) and in adults (K) of single worms whose DVA neuron is ablated by transgenic overexpression of CED-3 in DVA neuron (nlp-12 promoter) was analyzed in the indicated genotypes. Animals were analyzed by fluorescence microscopy after locomotion recordings to determine if DVA was ablated. The npr-1 locomotion defect during the L4/A lethargus, but not in adults, was partially suppressed in the transgenic animals in which DVA was ablated (-DVA). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (**, p <0.01; ***, p <0.001; ns, not significant).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4495980&req=5

pgen.1005359.g005: GLR-2 AMPA receptors are required for the npr-1 lethargus defect.Locomotion behavior of single worms during the L4/A lethargus (A-E and H-J) and in adults (F, K) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, H), average motile fraction (B, D, and I), and average locomotion velocity (C, E, F, J and K) are plotted. (A-C) The npr-1 locomotion defect during L4/A lethargus was suppressed by mutations inactivating glr-2 AMPA receptors, and partially reinstated by transgenes expressing GLR-2 in AIA (gcy-28(d) promoter) and DVA (nlp-12 promoter) neurons, but not in Ventral Cord Interneurons (V.C.I., glr-1 promoter) in glr-2;npr-1 double mutants using the indicated promoters. (D-E) glr-1 mutations had no suppressing effect. (F) glr-2 mutations did not block the increased locomotion in npr-1 adults. (G) mEPSCs were recorded from body wall muscles of the adult worms for the indicated genotypes. Summary data are shown. (G) glr-2 mutations did not block the increased mEPSC rate in npr-1 adults. (H-K) Locomotion behavior during the L4/A lethargus (H-J) and in adults (K) of single worms whose DVA neuron is ablated by transgenic overexpression of CED-3 in DVA neuron (nlp-12 promoter) was analyzed in the indicated genotypes. Animals were analyzed by fluorescence microscopy after locomotion recordings to determine if DVA was ablated. The npr-1 locomotion defect during the L4/A lethargus, but not in adults, was partially suppressed in the transgenic animals in which DVA was ablated (-DVA). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (**, p <0.01; ***, p <0.001; ns, not significant).
Mentions: To determine if increased ASH activity is sufficient to arouse locomotion, we analyzed locomotion after artificially depolarizing ASH neurons. For this experiment, we utilized transgenic animals that express rat TRPV1 capsaicin receptors in ASH neurons [24]. In these animals, capsaicin treatment evokes ASH-mediated avoidance behaviors [24]. A 5-hour capsaicin treatment had little effect on L4/A motile fraction and locomotion velocity [11], whereas capsaicin treatment significantly accelerated adult locomotion and increased aldicarb sensitivity (Figs 4I–5J and S2G Fig). These effects were not observed in animals lacking TRPV1 expression in ASH neurons (Fig 4I and 4J). Thus, forced ASH depolarization was sufficient to arouse adult but not lethargus locomotion. Collectively, these results suggest that diminished and heightened ASH activity is associated with locomotion quiescence and arousal respectively; however, the magnitude of ASH’s arousing effects differ between lethargus and adult animals.

Bottom Line: Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1.These sensory neurons accelerate locomotion via both neuropeptide and glutamate release.Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America; Biological and Biomedical Sciences program, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), and stretch sensing (DVA) neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states.

No MeSH data available.


Related in: MedlinePlus