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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

RID activity increase correlates with forward movements.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal. Normalized ratiometric signal changes (ΔF/F), as well as the raw fluorescence intensities of GCaMP and cherry are shown. ΔF/F was used to calculate changes in calcium activity for each animal. Changes in positions of fluorescent signals were used to calculate velocity and directionality. (B) RID activity as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Left panel, RID activity increased when animals transition from backward to fast forward locomotion. Right panel, RID activity decreased when animals transition from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition periods from backward to forward locomotion and vice versa. (C) Cross-correlation analyses between the change in RID activity and the change in velocity. Positive and negative slopes (Y-axis) indicate increase (Ca rise) and decrease (Ca decay) in RID, respectively. Positive and negative values on the X-axis indicate changes in velocity from backward to forward locomotion (acceleration) and from forward to backward locomotion (deceleration), respectively. For B and C, N = 10 animals/genotype. In C, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.008
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fig4: RID activity increase correlates with forward movements.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal. Normalized ratiometric signal changes (ΔF/F), as well as the raw fluorescence intensities of GCaMP and cherry are shown. ΔF/F was used to calculate changes in calcium activity for each animal. Changes in positions of fluorescent signals were used to calculate velocity and directionality. (B) RID activity as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Left panel, RID activity increased when animals transition from backward to fast forward locomotion. Right panel, RID activity decreased when animals transition from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition periods from backward to forward locomotion and vice versa. (C) Cross-correlation analyses between the change in RID activity and the change in velocity. Positive and negative slopes (Y-axis) indicate increase (Ca rise) and decrease (Ca decay) in RID, respectively. Positive and negative values on the X-axis indicate changes in velocity from backward to forward locomotion (acceleration) and from forward to backward locomotion (deceleration), respectively. For B and C, N = 10 animals/genotype. In C, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.008

Mentions: RID maintained low activity during reversals, and increased its activity during forward movement (Figure 4A,B). Increased calcium activity was observed in both the RID soma (Figure 4) and axon (Video 2). No other Pflp-14-positive neurons exhibited obvious activity change that correlated with forward movement. During the transition from reversals to forward movement, we consistently observed an activity rise in RID, typically with a significant lag (~10 s) in reaching its peak when compared to the velocity rise (Figure 4A). A decrease in RID activity was observed following the transition from forward movement to reversals (Figure 4A,B). There was significant correlation between the rate of velocity change (acceleration and deceleration, X-axis) and the change in RID activity (Ca2+ rise and decay, Y-axis), when animals transited between forward movement and reversals, respectively (Figure 4C; p<0.006 for forward to reversal; p=0.0007 for reversal to forward movement).10.7554/eLife.19887.008Figure 4.RID activity increase correlates with forward movements.


Neuroendocrine modulation sustains the C. elegans forward motor state
RID activity increase correlates with forward movements.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal. Normalized ratiometric signal changes (ΔF/F), as well as the raw fluorescence intensities of GCaMP and cherry are shown. ΔF/F was used to calculate changes in calcium activity for each animal. Changes in positions of fluorescent signals were used to calculate velocity and directionality. (B) RID activity as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Left panel, RID activity increased when animals transition from backward to fast forward locomotion. Right panel, RID activity decreased when animals transition from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition periods from backward to forward locomotion and vice versa. (C) Cross-correlation analyses between the change in RID activity and the change in velocity. Positive and negative slopes (Y-axis) indicate increase (Ca rise) and decrease (Ca decay) in RID, respectively. Positive and negative values on the X-axis indicate changes in velocity from backward to forward locomotion (acceleration) and from forward to backward locomotion (deceleration), respectively. For B and C, N = 10 animals/genotype. In C, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.008
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fig4: RID activity increase correlates with forward movements.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal. Normalized ratiometric signal changes (ΔF/F), as well as the raw fluorescence intensities of GCaMP and cherry are shown. ΔF/F was used to calculate changes in calcium activity for each animal. Changes in positions of fluorescent signals were used to calculate velocity and directionality. (B) RID activity as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Left panel, RID activity increased when animals transition from backward to fast forward locomotion. Right panel, RID activity decreased when animals transition from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition periods from backward to forward locomotion and vice versa. (C) Cross-correlation analyses between the change in RID activity and the change in velocity. Positive and negative slopes (Y-axis) indicate increase (Ca rise) and decrease (Ca decay) in RID, respectively. Positive and negative values on the X-axis indicate changes in velocity from backward to forward locomotion (acceleration) and from forward to backward locomotion (deceleration), respectively. For B and C, N = 10 animals/genotype. In C, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.008
Mentions: RID maintained low activity during reversals, and increased its activity during forward movement (Figure 4A,B). Increased calcium activity was observed in both the RID soma (Figure 4) and axon (Video 2). No other Pflp-14-positive neurons exhibited obvious activity change that correlated with forward movement. During the transition from reversals to forward movement, we consistently observed an activity rise in RID, typically with a significant lag (~10 s) in reaching its peak when compared to the velocity rise (Figure 4A). A decrease in RID activity was observed following the transition from forward movement to reversals (Figure 4A,B). There was significant correlation between the rate of velocity change (acceleration and deceleration, X-axis) and the change in RID activity (Ca2+ rise and decay, Y-axis), when animals transited between forward movement and reversals, respectively (Figure 4C; p<0.006 for forward to reversal; p=0.0007 for reversal to forward movement).10.7554/eLife.19887.008Figure 4.RID activity increase correlates with forward movements.

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