Calcium dynamics regulating the timing of decision-making in C. elegans
- Osaka University, Japan
- Tohoku Bunka Gakuen University, Japan
- The University of Edinburgh, United Kingdom
- Saitama University, Japan
- The University of Tokyo, Japan
- Ibaraki University, Japan
- Tohoku University, Japan
Figures
Figure 1 with 1 supplement
C.elegans selectively initiates runs away from the odor source.
(A) Examples of the tracks of 2 animals during 12 min of 2-nonanone avoidance assay, overlaid on a schematic drawing of a 9 cm plate. One of the tracks is magnified below. In the magnified view, …
Figure 1—figure supplement 1
Differences between 2-nonanone avoidance behavior and salt-taxis of C.elegans.
(A) Pirouettes and runs were classified by the length of turn interval (i.e., migratory durations). A distribution of turn intervals during the odor avoidance was fitted by the sum of two …
Figure 2 with 1 supplement
Pirouettes and runs are distinct behavioral states, which are associated with positive and negative dCworm/dt, respectively.
(A) Fitted odor gradient over the assay plate at 12 min, based on the actual measurements shown in Figure 2—figure supplement 1D. (B) (Top) Same with the magnified view of an animal's trajectory in F…
Figure 2—figure supplement 1
Measurement of the gaseous 2-nonanone gradient in the plate assay paradigm.
(A) A schematic cross-section (upper panel) and top view (lower panel) of gas sampling. The plate is placed upside-down. In the lower panel, crosses indicate positions of the odor source and dots …
Figure 3 with 1 supplement
AWB and ASH sensory neuron pairs regulate turning rate in response to dC/dt of 2-nonanone.
(A) Schematic drawing of the OSB2 system. (B) Behavioral response to temporal changes in the 2-nonanone concentration. (Top) Track of a wild-type animal. The first 60 s (gray) is a period of no odor …
Figure 3—figure supplement 1
Spatial arrangement of the odor stimulation and behavioral response in the OSB2 system.
(A) Arrangement of the odor flow on the OSB2 system. The end of the tube was positioned ~1 mm from the animal, and odor flow covered the entire body of the animal. Visualization was obtained from …
Figure 4 with 3 supplements
ASH neurons are activated according to dC/dt for initiating turns, and AWB neurons are activated according to the leaky integration of the negative dC/dt for suppressing turns with a dC/dt-dependent delay.
(A) ASH responses (middle panels) and turns (lower panels) in response to odor concentration increases from 0 to 1 μM in 45 s (left most; n = 32), 90 s (middle left; n = 39), 180 s (middle right; n =…
Figure 4—figure supplement 1
AWB responses were not fitted sufficiently by time-differential equations.
https://doi.org/10.7554/eLife.21629.014
Figure 4—figure supplement 2
Estimated intracellular calcium concentrations in AWB neurons calculated from measured ΔF/F0 in Figure 4B.
Estimated calcium concentration changes (black lines) in response to odor decreases from 1 to 0 μM in 45 s (left), 90 s (center), and 180 s (right) were also well-fitted by a leaky integrator …
Figure 4—figure supplement 3
ASH responses were partially fitted by the time-integral equations.
The ASH responses are the same as those in Figure 4A. Red arrows indicate the same timing with the red vertical dotted lines in Figure 4A. The parameters and goodness of fit are described in Table 3.
Figure 5
A computer model reproduced the directional choice in the odor avoidance task in a temporal integration-dependent manner.
(A) Model of the behavioral transition in 2-nonanone avoidance. During a pirouette, a model animal frequently repeated turns and short migrations. When a model animal initiated a migration away from …
Figure 6 with 1 supplement
Cell-autonomous computations in AWB neurons.
(A) The AWB responses of unc-13 (left) and unc-31 (right) mutants to the odor decreases, which are the same as those shown in the middle left panel of Figure 4B, were essentially similar to those of …
Figure 6—figure supplement 1
Responses of AWB and ASH neurons in odr-3 mutants.
(A) AWB responses in odr-3(n2150) (left panels; the same data as Figure 6B) or odr-3(n1605) (right panels; n = 28) mutants were fitted by the right-most equations. When fitting with the leaky …
Figure 7 with 1 supplement
Calcium channels are involved in the dynamic regulation of [Ca2+]i in a cell type-dependent manner.
(A and B) Responses of AWB (panel A) or ASH (panel B) neurons in strains with genetic and/or pharmacological suppression of N/P/Q-type VGCC UNC-2, T-type VGCC CCA-1, L-type VGCC EGL-19, IP3R ITR-1, …
Figure 7—figure supplement 1
ASH response does not depend on synaptic transmission.
ASH responses in wild-type (left; n = 35) and unc-13(e51) (right; n = 44) animals, analysed in parallel, are shown.
Figure 8
Physiological and molecular models of decision-making by C. elegans during odor avoidance.
(A) Computations of ASH and AWB neurons during odor avoidance behavior. (B) Model of the molecular mechanisms for temporal computation of odor information in AWB and ASH neurons. (Left) In AWB …
Videos
Video 1
Time-course changes in the fitted 2-nonanone concentration.
Although the odor sources were two circles of ~5 mm diameter in the real experiment, they were treated as points in the simulation.
Video 2
A demonstration video for calcium imaging with the OSB2 system.
(Left) The bright field images for the tracking and the fluorescence images for calcium imaging were acquired simultaneously but separately in the tracking and calcium imaging subsystems, …
Video 3
Visualization of the odor flow on the OSB2 system.
The view was from the ocular lens of the microscope. The tube end was on the left and the flow was from the left to the right, which was visualized by fog produced by Wizard Stick (Zero Toys, USA). …
Video 4
Optogenetic activation of AWB neurons.
After 60 s without any stimulus, a transgenic animal expressing the bistable variant of channelrhodopsin, ChR2(C128S), was illuminated with blue light for 3 s to cause sustained AWB activation, and …
Tables
Table 1
Models and parameters used in the fitting of ASH responses with time-differential equations.
| Conditions | ASH, wild-type | ASH, odr-3(n2150) | ASH, odr-3(n1605) | ASH, wild-type slow component | ||
|---|---|---|---|---|---|---|
| Durations of up/down phase | Up 45 s | Up 90 s | Up 180 s | Up 90 s | Up 90 s | Up 90 s |
| Model | ||||||
| Parameters used for fitting to ΔF/F0 | ||||||
| k | 56.1 [μM−1·s] | 80.9 [μM−1·s] | 121.9 [μM−1·s] | 49.1 [μM−1·s] | 46.7 [μM−1·s] | 2.96 [μM−1] |
| τ | - | - | - | - | - | 10.4 [s] |
| Parameters used for fitting to estimated calcium concentration | ||||||
| k | 3.9 [s] | 6.2 [s] | 7.9 [s] | 2.8 [s] | 2.9 [s] | - |
| τ | - | - | - | - | - | - |
| fmax | 9.4 | 9.5 | 9.2 | 9.1 | 8.7 | - |
| fmin | 0.79 | 0.79 | 0.77 | 0.76 | 0.73 | - |
| Xbase | 103.8 [nM] | 92.2 [nM] | 107.0 [nM] | 108.2 [nM] | 109.7 [nM] | - |
Table 2
Models and parameters used in the fitting of AWB responses with leaky integrator equations.
| Conditions | AWB, wild-type | AWB, unc-13(e51) | AWB, unc-31(e928) | AWB, odr-3(n2150) | AWB, odr-3(n1605) | ||
|---|---|---|---|---|---|---|---|
| Durations of up/down phase | Down 45 s | Down 90 s | Down 180 s | Down 90 s | Down 90 s | Down 90 s | Down 90 s |
| Model | |||||||
| (∆t = 67 s) | (∆t = 66 s) | ||||||
| Parameters used for fitting to ΔF/F0 | |||||||
| k | 4.6 [μM−1] | 3.6 [μM−1] | 3.0 [μM−1] | 2.6 [μM−1] | 4.9 [μM−1] | 8.7 [μM−1] | 7.7 [μM−1] |
| τ | 19.7 [s] | 28.1 [s] | 25.0 [s] | 34.5 [s] | 28.1 [s] | 25.2 [s] | 23.5 [s] |
| Parameters used for fitting to estimated calcium concentration | |||||||
| k | 0.40 | 0.37 | 0.33 | 0.26 | 0.44 | 1.00 | 0.87 |
| τ | 21.1 [s] | 28.5 [s] | 25.0 [s] | 37.3 [s] | 30.7 [s] | 17.7 [s] | 17.7 [s] |
| fmax | 9.7 | 10.1 | 8.5 | 9.6 | 8.9 | 10.9 | 10.4 |
| fmin | 0.81 | 0.84 | 0.71 | 0.80 | 0.74 | 0.91 | 0.87 |
| Xbase | 66.1 [nM] | 56.7 [nM] | 89.6 [nM] | 66.7 [nM] | 81.2 [nM] | 41.8 [nM] | 51.5 [nM] |
Table 3
Parameters and goodness of fit results for mathematical models of ASH and AWB responses.
| Conditions | ASH, wild-type | AWB, wild-type | ||||
|---|---|---|---|---|---|---|
| Durations of up/down phase | Up 45 s | Up 90 s | Up 180 s | Down 45 s | Down 90 s | Down 180 s |
| Number of samples (frames) used for calculation of BIC | N = 135 (t = −60 ~ 75 s) | N = 180 (t = −60 ~ 120 s) | N = 270 (t = −60 ~ 210 s) | N = 135 (t = −60 ~ 75 s) | N = 180 (t = −60 ~ 120 s) | N = 270 (t = −60 ~ 210 s) |
| k = 56.1 [μM−1·s] BIC = −222.2 | k = 80.9 [μM−1·s] BIC = −446.5 | k = 121.9 [μM−1·s] BIC = −637.8 | k = −58.4 [μM−1·s] BIC = −170.6 | k = −73.4 [μM−1·s] BIC = −372.5 | k = −67.3 [μM−1·s] BIC = −1157 | |
| k = 5.8 [μM−1] τ = 12.0 [s] BIC = −331.1 | k = 18.9 [μM−1] τ = 4.4 [s] BIC = −472.8 | k = 11.5 [μM−1] τ = 11.7 [s] BIC = −804.9 | k = −4.56 [μM−1] τ = 19.7 [s] BIC = −591.9 | k = −3.58 [μM−1] τ = 28.1 [s] BIC = −806.2 | k = −3.01 [μM−1] τ = 25.0 [s] BIC = −1458 | |
Table 4
Parameters and goodness of fit for mathematical models of AWB responses in odr-3 mutants.
| Conditions | AWB, odr-3(n2150) | AWB, odr-3(n1605) |
|---|---|---|
| Durations of up/down phase | down 90 s | down 90 s |
| Number of samples (frames) used for calculation of BIC | N = 180 (t = −60 ~ 120 s) | N = 180 (t = −60 ~ 120 s) |
| k = 89.1 [μM−1·s] BIC = 25.1 | k = 77.3 [μM−1·s] BIC = −39.2 | |
| k = 2.08 [μM−1] τ → ∞ BIC = −477.7 | k = 1.77 [μM−1] τ → ∞ BIC = −578.5 | |
| k = 8.71 [μM−1] τ = 25.2 [s] ∆t = 67 [s] BIC = −645.6 | k = 7.73 [μM−1] τ = 23.5 [s] ∆t = 66 [s] BIC = −779.9 |
Additional files
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Supplementary file 1
Detailed results of statistical tests in this study are shown.
- https://doi.org/10.7554/eLife.21629.027
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Supplementary file 2
Plasmids used in this study are shown.
- https://doi.org/10.7554/eLife.21629.028
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Supplementary file 3
Strains used in this study are shown.
- https://doi.org/10.7554/eLife.21629.029
