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Neuroendocrine modulation sustains the C. elegans forward motor state

View Article: PubMed Central - PubMed

ABSTRACT

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

Doi:: http://dx.doi.org/10.7554/eLife.19887.001

No MeSH data available.


Related in: MedlinePlus

Raw data for spontaneous motor behaviors of animals quantified in Figure 6A.Plots of the body curvature (Y axis, anterior to posterior) over time (X axis) of individual animals of the following genotypes: the single copy insertion of a fragment of the flp-14 genomic fragment in N2 background Si(FLP-14), flp-14, flp-14;Si(FLP-14), flp-14;unc-39, flp-14;unc-39;Si(FLP-14). Each heat-map plot represents one animal. N = 10 animals/genotype. These recordings were performed on the same day. They were recorded on the same plate, one animal at a time, alternating through animals of each genotype. Forward and reversal movements are viewed by the directionality of the curvature propagation; velocities are viewed by the speed of curvature propagation. White regions represent times when the program lost track of the animal, which typically happened when the animal’s head and tail touched each other during turns, or when the animal crawled to the edge of the plate. Si(FLP-14) restored flp-14 mutants’ defects and was similar to that of Si(FLP-14). flp-14;unc-39;Si(FLP-14) mutants exhibited severely reduced forward propensity, continuity, and velocity.DOI:http://dx.doi.org/10.7554/eLife.19887.016
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fig6s1: Raw data for spontaneous motor behaviors of animals quantified in Figure 6A.Plots of the body curvature (Y axis, anterior to posterior) over time (X axis) of individual animals of the following genotypes: the single copy insertion of a fragment of the flp-14 genomic fragment in N2 background Si(FLP-14), flp-14, flp-14;Si(FLP-14), flp-14;unc-39, flp-14;unc-39;Si(FLP-14). Each heat-map plot represents one animal. N = 10 animals/genotype. These recordings were performed on the same day. They were recorded on the same plate, one animal at a time, alternating through animals of each genotype. Forward and reversal movements are viewed by the directionality of the curvature propagation; velocities are viewed by the speed of curvature propagation. White regions represent times when the program lost track of the animal, which typically happened when the animal’s head and tail touched each other during turns, or when the animal crawled to the edge of the plate. Si(FLP-14) restored flp-14 mutants’ defects and was similar to that of Si(FLP-14). flp-14;unc-39;Si(FLP-14) mutants exhibited severely reduced forward propensity, continuity, and velocity.DOI:http://dx.doi.org/10.7554/eLife.19887.016

Mentions: Like RID-ablated or unc-39 animals, flp-14 mutants replaced long foraging with shortened forward runs and more frequent pauses and reversals (Figure 5A–A’’; Figure 5—figure supplement 1; Video 5). flp-14 mutants exhibited a reduced severity in their defects: the reduction of mean duration of forward runs, and the increase of re-initiation frequency of forward and reversal movements were less prominent as the RID-ablated or unc-39 mutant animals. The mean forward and reversal velocity, reduced in both RID ablated and unc-39 mutant animals, did not exhibit a statistically significant change in flp-14 mutants (Figure 5A–A”’; Figure 5—figure supplements 1 and 2). Expressing a single copy of the wild-type flp-14 genomic fragment Si(FLP-14) in flp-14 mutants led to an increase in the duration of the forward runs and a decrease of the re-initiation frequency for both forward and reversal movements (Figure 6A–A”’, B–B”’; Figure 6—figure supplements 1 and 2). The rescue of these motor defects confirms the functional requirement of FLP-14 in sustaining forward locomotion.10.7554/eLife.19887.015Figure 6.FLP-14 potentiates forward movements through RID.


Neuroendocrine modulation sustains the C. elegans forward motor state
Raw data for spontaneous motor behaviors of animals quantified in Figure 6A.Plots of the body curvature (Y axis, anterior to posterior) over time (X axis) of individual animals of the following genotypes: the single copy insertion of a fragment of the flp-14 genomic fragment in N2 background Si(FLP-14), flp-14, flp-14;Si(FLP-14), flp-14;unc-39, flp-14;unc-39;Si(FLP-14). Each heat-map plot represents one animal. N = 10 animals/genotype. These recordings were performed on the same day. They were recorded on the same plate, one animal at a time, alternating through animals of each genotype. Forward and reversal movements are viewed by the directionality of the curvature propagation; velocities are viewed by the speed of curvature propagation. White regions represent times when the program lost track of the animal, which typically happened when the animal’s head and tail touched each other during turns, or when the animal crawled to the edge of the plate. Si(FLP-14) restored flp-14 mutants’ defects and was similar to that of Si(FLP-14). flp-14;unc-39;Si(FLP-14) mutants exhibited severely reduced forward propensity, continuity, and velocity.DOI:http://dx.doi.org/10.7554/eLife.19887.016
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fig6s1: Raw data for spontaneous motor behaviors of animals quantified in Figure 6A.Plots of the body curvature (Y axis, anterior to posterior) over time (X axis) of individual animals of the following genotypes: the single copy insertion of a fragment of the flp-14 genomic fragment in N2 background Si(FLP-14), flp-14, flp-14;Si(FLP-14), flp-14;unc-39, flp-14;unc-39;Si(FLP-14). Each heat-map plot represents one animal. N = 10 animals/genotype. These recordings were performed on the same day. They were recorded on the same plate, one animal at a time, alternating through animals of each genotype. Forward and reversal movements are viewed by the directionality of the curvature propagation; velocities are viewed by the speed of curvature propagation. White regions represent times when the program lost track of the animal, which typically happened when the animal’s head and tail touched each other during turns, or when the animal crawled to the edge of the plate. Si(FLP-14) restored flp-14 mutants’ defects and was similar to that of Si(FLP-14). flp-14;unc-39;Si(FLP-14) mutants exhibited severely reduced forward propensity, continuity, and velocity.DOI:http://dx.doi.org/10.7554/eLife.19887.016
Mentions: Like RID-ablated or unc-39 animals, flp-14 mutants replaced long foraging with shortened forward runs and more frequent pauses and reversals (Figure 5A–A’’; Figure 5—figure supplement 1; Video 5). flp-14 mutants exhibited a reduced severity in their defects: the reduction of mean duration of forward runs, and the increase of re-initiation frequency of forward and reversal movements were less prominent as the RID-ablated or unc-39 mutant animals. The mean forward and reversal velocity, reduced in both RID ablated and unc-39 mutant animals, did not exhibit a statistically significant change in flp-14 mutants (Figure 5A–A”’; Figure 5—figure supplements 1 and 2). Expressing a single copy of the wild-type flp-14 genomic fragment Si(FLP-14) in flp-14 mutants led to an increase in the duration of the forward runs and a decrease of the re-initiation frequency for both forward and reversal movements (Figure 6A–A”’, B–B”’; Figure 6—figure supplements 1 and 2). The rescue of these motor defects confirms the functional requirement of FLP-14 in sustaining forward locomotion.10.7554/eLife.19887.015Figure 6.FLP-14 potentiates forward movements through RID.

View Article: PubMed Central - PubMed

ABSTRACT

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

Doi:: http://dx.doi.org/10.7554/eLife.19887.001

No MeSH data available.


Related in: MedlinePlus