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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.


Frequency distribution of forward and reversal velocities quantified in Figure 5.Percentage distribution of forward and reversal velocities of individual animals of the following genotypes: hpIs202 (Pceh-10-GFP RID marker) mock-ablated, hpIs202 (Pceh-10-GFP RID marker) RID-ablated, wild-type (N2), unc-39, flp-14, ins-17, and ins-17 flp-14. Negative values represent reversal velocity; positive values represent forward velocity; zero value represents pauses. Compared to their respective controls, RID-ablated and unc-39 mutants exhibited reduced velocities, specifically during forward locomotion. flp-14 and ins-17 flp-14 mutants showed a tendency towards reduced velocities, while ins-17 mutants were similar to wild-type (N2). N = 10 animals/genotype.DOI:http://dx.doi.org/10.7554/eLife.19887.012
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fig5s2: Frequency distribution of forward and reversal velocities quantified in Figure 5.Percentage distribution of forward and reversal velocities of individual animals of the following genotypes: hpIs202 (Pceh-10-GFP RID marker) mock-ablated, hpIs202 (Pceh-10-GFP RID marker) RID-ablated, wild-type (N2), unc-39, flp-14, ins-17, and ins-17 flp-14. Negative values represent reversal velocity; positive values represent forward velocity; zero value represents pauses. Compared to their respective controls, RID-ablated and unc-39 mutants exhibited reduced velocities, specifically during forward locomotion. flp-14 and ins-17 flp-14 mutants showed a tendency towards reduced velocities, while ins-17 mutants were similar to wild-type (N2). N = 10 animals/genotype.DOI:http://dx.doi.org/10.7554/eLife.19887.012

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
Frequency distribution of forward and reversal velocities quantified in Figure 5.Percentage distribution of forward and reversal velocities of individual animals of the following genotypes: hpIs202 (Pceh-10-GFP RID marker) mock-ablated, hpIs202 (Pceh-10-GFP RID marker) RID-ablated, wild-type (N2), unc-39, flp-14, ins-17, and ins-17 flp-14. Negative values represent reversal velocity; positive values represent forward velocity; zero value represents pauses. Compared to their respective controls, RID-ablated and unc-39 mutants exhibited reduced velocities, specifically during forward locomotion. flp-14 and ins-17 flp-14 mutants showed a tendency towards reduced velocities, while ins-17 mutants were similar to wild-type (N2). N = 10 animals/genotype.DOI:http://dx.doi.org/10.7554/eLife.19887.012
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Related In: Results  -  Collection

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fig5s2: Frequency distribution of forward and reversal velocities quantified in Figure 5.Percentage distribution of forward and reversal velocities of individual animals of the following genotypes: hpIs202 (Pceh-10-GFP RID marker) mock-ablated, hpIs202 (Pceh-10-GFP RID marker) RID-ablated, wild-type (N2), unc-39, flp-14, ins-17, and ins-17 flp-14. Negative values represent reversal velocity; positive values represent forward velocity; zero value represents pauses. Compared to their respective controls, RID-ablated and unc-39 mutants exhibited reduced velocities, specifically during forward locomotion. flp-14 and ins-17 flp-14 mutants showed a tendency towards reduced velocities, while ins-17 mutants were similar to wild-type (N2). N = 10 animals/genotype.DOI:http://dx.doi.org/10.7554/eLife.19887.012
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.