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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

Glutamate released by sensory neurons is required for the npr-1 locomotion and the cholinergic transmission defects.Locomotion behavior of single worms during the L4/A lethargus (A-C) and in adults (D-E) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, D), average motile fraction (B), and average locomotion velocity (C, E) are plotted. The npr-1 locomotion defect was suppressed by mutations inactivating EAT-4/VGLUT, and partially reinstated by transgenes expressing EAT-4 in ASH neurons (sra-6 promoter) and touch neurons (mec-4 promoter) in eat-4;npr-1 double mutants using the indicated promoters. An EAT-4 transgene expressed in ASK neurons (sra-9 promoter) lacked rescuing activity. (F) The npr-1 aldicarb hypersensitivity was suppressed by mutations inactivating EAT-4/VGLUT. The percentage of animals paralyzed on 1 mM aldicarb at 80 min were plotted for the indicated genotypes. The number of trials is indicated for each genotype. Full time courses of aldicarb-inuced paralysis are shown in S2F Fig. (G-I) The npr-1 cholinergic transmission defect was abolished by mutations inactivating EAT-4/VGLUT. mEPSCs were recorded from body wall muscles of adult worms for the indicated genotypes. Representative traces of mEPSCs (G) and summary data are shown (H-I). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (*, p <0.05; **, p <0.01; ***, p <0.001; ns, not significant).
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pgen.1005359.g003: Glutamate released by sensory neurons is required for the npr-1 locomotion and the cholinergic transmission defects.Locomotion behavior of single worms during the L4/A lethargus (A-C) and in adults (D-E) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, D), average motile fraction (B), and average locomotion velocity (C, E) are plotted. The npr-1 locomotion defect was suppressed by mutations inactivating EAT-4/VGLUT, and partially reinstated by transgenes expressing EAT-4 in ASH neurons (sra-6 promoter) and touch neurons (mec-4 promoter) in eat-4;npr-1 double mutants using the indicated promoters. An EAT-4 transgene expressed in ASK neurons (sra-9 promoter) lacked rescuing activity. (F) The npr-1 aldicarb hypersensitivity was suppressed by mutations inactivating EAT-4/VGLUT. The percentage of animals paralyzed on 1 mM aldicarb at 80 min were plotted for the indicated genotypes. The number of trials is indicated for each genotype. Full time courses of aldicarb-inuced paralysis are shown in S2F Fig. (G-I) The npr-1 cholinergic transmission defect was abolished by mutations inactivating EAT-4/VGLUT. mEPSCs were recorded from body wall muscles of adult worms for the indicated genotypes. Representative traces of mEPSCs (G) and summary data are shown (H-I). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (*, p <0.05; **, p <0.01; ***, p <0.001; ns, not significant).

Mentions: Many C. elegans sensory neurons are glutamatergic, including two neurons in the RMG circuit (ASH and ASK) and the body touch neurons [23]. To determine if glutamate release by sensory neurons is required for accelerated locomotion in npr-1 mutants, we analyzed mutations that inactivate the vesicular glutamate transporter (eat-4 VGLUT), which is primarily expressed in sensory neurons [23]. eat-4 VGLUT mutations blocked the increased motile fraction and locomotion speed of npr-1 mutants both during the L4-Adult (L4/A) molt (Fig 3A–3C) and in adults (Fig 3D and 3E). eat-4 mutations also blocked the hypersensitivity to aldicarb (Fig 3F and S2F Fig) and increased mEPSC rate (Fig 3G and 3H) defects of npr-1 adults. Transgenes restoring EAT-4 expression in touch neurons and ASH neurons partially reinstated both lethargus (Fig 3B and 3C) and adult locomotion (Fig 3D and 3E) defects in eat-4; npr-1 double mutants, whereas transgenes expressed in ASK lacked rescuing activity (Fig 3B and 3C). eat-4 transgenes had no effect on lethargus quiescence in wild type animals (S3 Fig). These results suggest that glutamate released by ASH and touch neurons arouses locomotion in L4/A and adult npr-1 mutants.


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)

Glutamate released by sensory neurons is required for the npr-1 locomotion and the cholinergic transmission defects.Locomotion behavior of single worms during the L4/A lethargus (A-C) and in adults (D-E) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, D), average motile fraction (B), and average locomotion velocity (C, E) are plotted. The npr-1 locomotion defect was suppressed by mutations inactivating EAT-4/VGLUT, and partially reinstated by transgenes expressing EAT-4 in ASH neurons (sra-6 promoter) and touch neurons (mec-4 promoter) in eat-4;npr-1 double mutants using the indicated promoters. An EAT-4 transgene expressed in ASK neurons (sra-9 promoter) lacked rescuing activity. (F) The npr-1 aldicarb hypersensitivity was suppressed by mutations inactivating EAT-4/VGLUT. The percentage of animals paralyzed on 1 mM aldicarb at 80 min were plotted for the indicated genotypes. The number of trials is indicated for each genotype. Full time courses of aldicarb-inuced paralysis are shown in S2F Fig. (G-I) The npr-1 cholinergic transmission defect was abolished by mutations inactivating EAT-4/VGLUT. mEPSCs were recorded from body wall muscles of adult worms for the indicated genotypes. Representative traces of mEPSCs (G) and summary data are shown (H-I). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (*, p <0.05; **, p <0.01; ***, p <0.001; ns, not significant).
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Related In: Results  -  Collection

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pgen.1005359.g003: Glutamate released by sensory neurons is required for the npr-1 locomotion and the cholinergic transmission defects.Locomotion behavior of single worms during the L4/A lethargus (A-C) and in adults (D-E) was analyzed in the indicated genotypes. Instantaneous locomotion velocity (A, D), average motile fraction (B), and average locomotion velocity (C, E) are plotted. The npr-1 locomotion defect was suppressed by mutations inactivating EAT-4/VGLUT, and partially reinstated by transgenes expressing EAT-4 in ASH neurons (sra-6 promoter) and touch neurons (mec-4 promoter) in eat-4;npr-1 double mutants using the indicated promoters. An EAT-4 transgene expressed in ASK neurons (sra-9 promoter) lacked rescuing activity. (F) The npr-1 aldicarb hypersensitivity was suppressed by mutations inactivating EAT-4/VGLUT. The percentage of animals paralyzed on 1 mM aldicarb at 80 min were plotted for the indicated genotypes. The number of trials is indicated for each genotype. Full time courses of aldicarb-inuced paralysis are shown in S2F Fig. (G-I) The npr-1 cholinergic transmission defect was abolished by mutations inactivating EAT-4/VGLUT. mEPSCs were recorded from body wall muscles of adult worms for the indicated genotypes. Representative traces of mEPSCs (G) and summary data are shown (H-I). The number of animals analyzed is indicated for each genotype. Error bars indicate SEM. Values that differ significantly are indicated (*, p <0.05; **, p <0.01; ***, p <0.001; ns, not significant).
Mentions: Many C. elegans sensory neurons are glutamatergic, including two neurons in the RMG circuit (ASH and ASK) and the body touch neurons [23]. To determine if glutamate release by sensory neurons is required for accelerated locomotion in npr-1 mutants, we analyzed mutations that inactivate the vesicular glutamate transporter (eat-4 VGLUT), which is primarily expressed in sensory neurons [23]. eat-4 VGLUT mutations blocked the increased motile fraction and locomotion speed of npr-1 mutants both during the L4-Adult (L4/A) molt (Fig 3A–3C) and in adults (Fig 3D and 3E). eat-4 mutations also blocked the hypersensitivity to aldicarb (Fig 3F and S2F Fig) and increased mEPSC rate (Fig 3G and 3H) defects of npr-1 adults. Transgenes restoring EAT-4 expression in touch neurons and ASH neurons partially reinstated both lethargus (Fig 3B and 3C) and adult locomotion (Fig 3D and 3E) defects in eat-4; npr-1 double mutants, whereas transgenes expressed in ASK lacked rescuing activity (Fig 3B and 3C). eat-4 transgenes had no effect on lethargus quiescence in wild type animals (S3 Fig). These results suggest that glutamate released by ASH and touch neurons arouses locomotion in L4/A and adult npr-1 mutants.

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