Limits...
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

The loss of PVC or AVB alone does not abolish RID activity rise during forward movement.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal with PVC (and other neurons) ablated. Normalized ratiometric (GCaMP/Cherry) 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 in PVC (and other neurons)- ablated animals as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Top panel, RID activity increased when animals transitioned from backward to fast forward locomotion. Bottom panel, RID activity decreased when animals transitioned from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition period from backward to forward locomotion and vice versa (C, D). The same analyses as in A and B, except that experiments were performed in animals where AVB (and other neurons) were ablated. (E, F) Cross-correlation analyses between the change in RID activity, and the change in velocity in PVC (and other neurons)- (E) and AVB (and other neurons)-ablated animals (F). Positive and negative slopes (Y-axis) indicate increase (Calcium Rise) and decrease (Calcium Decay) in RID activity, 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, D, E and F, N = 9–10 animals/genotype. In E and F, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.024
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120884&req=5

fig8s1: The loss of PVC or AVB alone does not abolish RID activity rise during forward movement.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal with PVC (and other neurons) ablated. Normalized ratiometric (GCaMP/Cherry) 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 in PVC (and other neurons)- ablated animals as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Top panel, RID activity increased when animals transitioned from backward to fast forward locomotion. Bottom panel, RID activity decreased when animals transitioned from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition period from backward to forward locomotion and vice versa (C, D). The same analyses as in A and B, except that experiments were performed in animals where AVB (and other neurons) were ablated. (E, F) Cross-correlation analyses between the change in RID activity, and the change in velocity in PVC (and other neurons)- (E) and AVB (and other neurons)-ablated animals (F). Positive and negative slopes (Y-axis) indicate increase (Calcium Rise) and decrease (Calcium Decay) in RID activity, 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, D, E and F, N = 9–10 animals/genotype. In E and F, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.024

Mentions: A full elucidation of the functional connectivity of RID awaits future investigation (Figure 8E), as our current exploration indicates complexity. Two main reported inputs to RID in the adult wiring diagram are the premotor interneurons of the forward motor circuit, PVC and AVB, (White et al., 1986). Such a circuit disposition would allow RID to function downstream of the forward-driving premotor interneurons to promote forward bouts. Ablation of PVC and AVB separately (and with other interneurons); however, did not abolish the RID’s activity rise during, or coordination with, forward movement (Figure 8—figure supplement 1A,B,E). They may act redundantly, or additional inputs may activate RID. A full EM reconstruction of RID in adults is required.


Neuroendocrine modulation sustains the C. elegans forward motor state
The loss of PVC or AVB alone does not abolish RID activity rise during forward movement.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal with PVC (and other neurons) ablated. Normalized ratiometric (GCaMP/Cherry) 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 in PVC (and other neurons)- ablated animals as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Top panel, RID activity increased when animals transitioned from backward to fast forward locomotion. Bottom panel, RID activity decreased when animals transitioned from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition period from backward to forward locomotion and vice versa (C, D). The same analyses as in A and B, except that experiments were performed in animals where AVB (and other neurons) were ablated. (E, F) Cross-correlation analyses between the change in RID activity, and the change in velocity in PVC (and other neurons)- (E) and AVB (and other neurons)-ablated animals (F). Positive and negative slopes (Y-axis) indicate increase (Calcium Rise) and decrease (Calcium Decay) in RID activity, 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, D, E and F, N = 9–10 animals/genotype. In E and F, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.024
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120884&req=5

fig8s1: The loss of PVC or AVB alone does not abolish RID activity rise during forward movement.(A) Representative velocity (top) and corresponding RID calcium activity trace (bottom) from a freely moving animal with PVC (and other neurons) ablated. Normalized ratiometric (GCaMP/Cherry) 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 in PVC (and other neurons)- ablated animals as measured by GCaMP/cherry ratio change (± SEM) during transition periods. Top panel, RID activity increased when animals transitioned from backward to fast forward locomotion. Bottom panel, RID activity decreased when animals transitioned from forward to backward locomotion. For A and B, dotted longitudinal lines indicate transition period from backward to forward locomotion and vice versa (C, D). The same analyses as in A and B, except that experiments were performed in animals where AVB (and other neurons) were ablated. (E, F) Cross-correlation analyses between the change in RID activity, and the change in velocity in PVC (and other neurons)- (E) and AVB (and other neurons)-ablated animals (F). Positive and negative slopes (Y-axis) indicate increase (Calcium Rise) and decrease (Calcium Decay) in RID activity, 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, D, E and F, N = 9–10 animals/genotype. In E and F, each dot represents a transitional event.DOI:http://dx.doi.org/10.7554/eLife.19887.024
Mentions: A full elucidation of the functional connectivity of RID awaits future investigation (Figure 8E), as our current exploration indicates complexity. Two main reported inputs to RID in the adult wiring diagram are the premotor interneurons of the forward motor circuit, PVC and AVB, (White et al., 1986). Such a circuit disposition would allow RID to function downstream of the forward-driving premotor interneurons to promote forward bouts. Ablation of PVC and AVB separately (and with other interneurons); however, did not abolish the RID’s activity rise during, or coordination with, forward movement (Figure 8—figure supplement 1A,B,E). They may act redundantly, or additional inputs may activate RID. A full EM reconstruction of RID in adults is required.

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