Dimorphic neural network architecture prioritizes sexual-related behaviors in male Caenorhabditis elegans
- Department of Systems Science, Faculty of Arts and Sciences, Beijing Normal University, China
- International Academic Center of Complex Systems, Beijing Normal University, China
- School of Systems Science, Beijing Normal University, China
- Huitong College, Beijing Normal University, China
- Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, China
- Department of Neuroscience, City University of Hong Kong, China
Figures
Figure 1 with 5 supplements
Structural characteristics of neural networks in male and hermaphrodite.
(A) The node strengths follow exponential distribution in both neural networks. (B) Neurons in the male neural network exhibit significantly more node strengths in comparison with those in the hermaphrodite. (C) Sex-specific neurons exhibit significantly more node strengths in comparison with sex-shared neurons in the male neural network. (D) Sex-specific neurons exhibit similar node strengths in comparison with sex-shared neurons in the hermaphrodite neural network. (E) Prediction of behavioral outputs based on the top 20 node strengths in male and hermaphrodite neural networks. (F) The node out-strengths follow exponential distribution in both neural networks. (G) Neurons in the male neural network exhibit significantly more node out-strengths in comparison with those in the hermaphrodite. (H) Sex-specific neurons exhibit significantly more node out-strengths in comparison with sex-shared neurons in the male neural network. (I) Sex-specific neurons exhibit similar node out-strengths in comparison with sex-shared neurons in the hermaphrodite neural network. (J) The node in-strengths follow exponential distribution in both neural networks. (K) Neurons in the male neural network exhibit slightly more node in-strengths in comparison with those in the hermaphrodite. (L) Sex-specific neurons exhibit significantly more node in-strengths in comparison with sex-shared neurons in the male neural network. (M) Sex-specific neurons exhibit significantly less node in-strengths in comparison with sex-shared neurons in the hermaphrodite neural network. (N) Neurons in the male neural network exhibit significantly more edge weights in comparison with those in the hermaphrodite. (O) Sex-specific neurons exhibit similar edge weights in comparison with sex-shared neurons in the male neural network. (P) Sex-specific neurons exhibit significantly less edge weights in comparison with sex-shared neurons in the hermaphrodite neural network. (Q) Neurons in the male neural network exhibit significantly shorter length of the shortest path in comparison with those in the hermaphrodite. (R) Sex-specific neurons exhibit significantly shorter length of the shortest path in comparison with sex-shared neurons in the male neural network. (S) Sex-specific neurons exhibit similar length of the shortest path in comparison with sex-shared neurons in the hermaphrodite neural network. (T) Neurons in the male neural network exhibit significantly lower betweenness centrality in comparison with those in the hermaphrodite. (U) Sex-specific neurons exhibit significantly lower betweenness centrality in comparison with sex-shared neurons in the male neural network. (V) Sex-specific neurons exhibit significantly lower betweenness centrality in comparison with sex-shared neurons in the hermaphrodite neural network. (W) Prediction of behavioral outputs based on the top 20 betweenness centrality in male and hermaphrodite neural networks. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 1—figure supplement 1
Directed-weighted graphs of male and hermaphrodite neural networks.
(A) The graph of hermaphrodite neural network. (B) The graph of male neural network.
Figure 1—figure supplement 2
The majority of neurons are shared in male and hermaphrodite neural networks.
Figure 1—figure supplement 3
Weight comparison for the top edges in male neural network, including ALA, AVA, and RIA-related edges.
Figure 1—figure supplement 4
Predicted circuits for sensorimotor integration in males (A) and hermaphrodites (B).
Figure 1—figure supplement 5
An artificial network as an example to demonstrate the calculation of each graph theory parameter.
(A) represents the topology diagram and (B) represents the connection matrix of the network.
Figure 2 with 2 supplements
Structural characteristics of sex-specific sub-neural networks in male and hermaphrodite.
(A) The node strengths follow exponential distribution in both sex-specific sub-neural networks. (B) Neurons in the male sex-specific sub-neural network exhibit significantly more node strengths in comparison with those in the hermaphrodite. (C) Sex-specific neurons exhibit significantly more node strengths in comparison with sex-shared neurons in the male sex-specific sub-neural network. (D) Sex-specific neurons exhibit similar node strengths in comparison with sex-shared neurons in the hermaphrodite sex-specific sub-neural network. (E) The node out-strengths follow exponential distribution in both sex-specific sub-neural networks. (F) Neurons in the male sex-specific sub-neural network exhibit significantly more node out-strengths in comparison with those in the hermaphrodite. (G) Sex-specific neurons exhibit significantly more node out-strengths in comparison with sex-shared neurons in the male sex-specific sub-neural network. (H) Sex-specific neurons exhibit similar node out-strengths in comparison with sex-shared neurons in the hermaphrodite sex-specific sub-neural network. (I) The node in-strengths follow exponential distribution in both sex-specific sub-neural networks. (J) Neurons in the male sex-specific sub-neural network exhibit significantly more node in-strengths in comparison with those in the hermaphrodite. (K) Sex-specific neurons exhibit slightly more node in-strengths in comparison with sex-shared neurons in the male sex-specific sub-neural network. (L) Sex-specific neurons exhibit similar node in-strengths in comparison with sex-shared neurons in the hermaphrodite sex-specific sub-neural network. (M) Neurons in the male sex-specific sub-neural network exhibit significantly more edge weights in comparison with those in the hermaphrodite. (N) Sex-specific neurons exhibit slightly less edge weights in comparison with sex-shared neurons in the male sex-specific sub-neural network. (O) Sex-specific neurons exhibit significantly less edge weights in comparison with sex-shared neurons in the hermaphrodite sex-specific sub-neural network. (P) Neurons in the male sex-specific sub-neural network exhibit significantly shorter length of the shortest path in comparison with those in the hermaphrodite. (Q) Sex-specific neurons exhibit significantly shorter length of the shortest path in comparison with sex-shared neurons in the male sex-specific sub-neural network. (R) Sex-specific neurons exhibit significantly longer length of the shortest path in comparison with sex-shared neurons in the hermaphrodite sex-specific sub-neural network. (S) Neurons in the male sex-specific sub-neural network exhibit significantly lower betweenness centrality in comparison with those in the hermaphrodite. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 2—figure supplement 1
Sex-specific sub-neural networks of hermaphrodite (A) and male (B).
Figure 2—figure supplement 2
Predicted male-specific (A) and hermaphrodite-specific (B) circuits.
Figure 3 with 1 supplement
Structural characteristics of sex-shared sub-neural networks in male and hermaphrodite.
(A) The node strengths follow exponential distribution in both sex-shared sub-neural networks. (B) Neurons in the male sex-shared sub-neural network exhibit similar node strengths in comparison with those in the hermaphrodite. (C) Node strength differences of the same neurons in two sex-shared sub-neural networks, positive represents more strength in male. (D) The node out-strengths follow exponential distribution in both sex-shared sub-neural networks. (E) Neurons in the male sex-shared sub-neural network exhibit similar node out-strengths in comparison with those in the hermaphrodite. (F) Node out-strength differences of the same neurons in two sex-shared sub-neural networks, positive represents more strength in male. (G) The node in-strengths follow exponential distribution in both sex-shared sub-neural networks. (H) Neurons in the male sex-shared sub-neural network exhibit similar node in-strengths in comparison with those in the hermaphrodite. (I) Node in-strength differences of the same neurons in two sex-shared sub-neural networks, positive represents more strength in male. (J) Top 5 male-specific and hermaphrodite-specific edges. (K) Neurons in the male sex-shared sub-neural network exhibit significantly more edge weights in comparison with those in the hermaphrodite. (L) Weight differences of the connection between same neurons in two sex-shared sub-neural networks, positive represents more strength in male. (M) Neurons in the male sex-shared sub-neural network exhibit significantly shorter length of the shortest path in comparison with those in the hermaphrodite. (N) Length differences of the shortest length between same neurons in two sex-shared sub-neural networks, positive represents longer length in male. (O) Neurons in the male sex-shared sub-neural network exhibit significantly lower betweenness centrality in comparison with those in the hermaphrodite. (P) Betweenness centrality differences of the same neurons in two sex-shared sub-neural networks, positive represents larger betweenness centrality in male. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 3—figure supplement 1
Sex-shared sub-neural networks of hermaphrodite (A) and male (B).
Figure 4
Dynamical characteristics of neural networks in male and hermaphrodite.
(A) Showcase of AVA neuron in hermaphrodite, left represents protocol of manipulating AVA membrane potential, right represents diverse membrane potential dynamics of all the other neurons in hermaphrodite neural network. (B) Downstream neurons with the strongest responses, pink color represents the same strongest response downstream neurons in two neural networks. Blue color represents strongest response downstream neurons in male, red color represents strongest response downstream neurons in hermaphrodite. (C) Sum of membrane potential changes in all the other neurons accesses individual neuron’s role as upstream neuron in a neural network. Neurons in the male neural network exhibit stronger influence as upstream neuron in comparison with those in the hermaphrodite. (D) Sex-specific neurons exhibit significantly higher membrane potential changes in all the other neurons in comparison with sex-shared neurons in the male neural network. (E) Sex-specific neurons exhibit similar membrane potential changes in all the other neurons in comparison with sex-shared neurons in the hermaphrodite neural network. (F) Prediction of behavioral outputs based on the top 20 neurons as upstream in male and hermaphrodite neural networks. (G) Sum of membrane potential changes in a neuron when activating all the other neurons accesses individual neuron’s role as downstream neuron in a neural network. Neurons in the male neural network exhibit stronger influence as downstream neuron in comparison with those in the hermaphrodite. (H) Sex-specific neurons exhibit significantly higher membrane potential changes when activating all the other neurons in comparison with sex-shared neurons in the male neural network. (I) Sex-specific neurons exhibit similar membrane potential changes when activating all the other neurons in comparison with sex-shared neurons in the hermaphrodite neural network. (J) Prediction of behavioral outputs based on the top 20 neurons as downstream in male and hermaphrodite neural networks. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 5 with 1 supplement
Males reveal consistently high local search behavior.
Reversal rate within a 10-minute time window for N2 wild-type males and hermaphrodites on 3.5 cm OP50-seeded plates under three conditions: (A) Thick food (10 µL E. coli OP50 cultured for 16 hours). (B) Thin food (10 µL E. coli OP50 cultured for 0.5 hours). (C) No food. (D) Statistical testing for the average reversal rate between minutes 7–10 under Thick food, Thin food, and No food conditions, with sample sizes of 17, 23, and 21 respectively. (E) Statistical testing for the average reversal rate between minutes 7–10 under different developmental stages, Sample size: 17 males and 14 hermaphrodites in L4 stage; 20 males and 25 hermaphrodites in 1-day adult stage; 2-day adult: 16 males and 15 hermaphrodites in 2-day adult stage. (F) Statistical testing for the average reversal rate between minutes 7–10 with different social experiences, with sample sizes of 20 for each group. (G) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds. 25 wild-type worms, 25 AVA::HisCl1 transgenic worms, and 21 non-transgenic siblings. (H) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds. 15 Wild-type worms, 15 AVA::HisCl1 transgenic worms, and 18 non-transgenic siblings. (I) Showcases of spontaneous calcium events in AVA of male and hermaphrodite 1-day adults. (J) Statistical testing for the spontaneous calcium event frequency in AVA of male and hermaphrodite 1-day adults. Sample size: 16 males and 13 hermaphrodites. (K) Hermaphrodite preference assay behavior paradigm. (L) Statistical testing for the choice index of 1-day adult males under different genetic backgrounds, with sample sizes of 11 for each group. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 5—figure supplement 1
Similar calcium event frequency of AVA in males (A) and hermaphrodites (B) L4 stage.
Sample size: 13 males and 13 hermaphrodites.
Figure 6 with 3 supplements
Neurons that are responsible for the increased local search in males.
(A) Chemical synapse number difference of AVA with upstream neurons between male and hermaphrodite. (B) A circuit with AVA and top 3 upstream neurons and top 4 downstream neurons based on the chemical synapse number difference. (C) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for RIC neuron manipulation. 17 wild-type worms, 20 RIC::TeTx transgenic worms, and 20 non-transgenic siblings. (D) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for RIC neuron manipulation. 15 wild-type worms, 20 RIC::TeTx transgenic worms, and 15 non-transgenic siblings. (E) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for DVC neuron manipulation. 15 wild-type worms, 20 DVC::TeTx transgenic worms, and 15 non-transgenic siblings. (F) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for DVC neuron manipulation. 20 wild-type worms, 20 DVC::TeTx transgenic worms, and 18 non-transgenic siblings. (G) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for PQR neuron manipulation. 17 wild-type worms, 20 PQR::TeTx transgenic worms, and 20 non-transgenic siblings. (H) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for PQR neuron manipulation. 14 wild-type worms, 15 PQR::TeTx transgenic worms, and 14 non-transgenic siblings. (I) Statistical testing for the spontaneous calcium event frequency in AVA of 1-day adult males under different genetic backgrounds for RIC neuron manipulation. 11 wild-type worms, 20 RIC::TeTx transgenic worms, and 15 non-transgenic siblings. (J) Statistical testing for the spontaneous calcium event frequency in AVA of 1-day adult hermaphrodites under different genetic backgrounds for RIC neuron manipulation. 8 wild-type worms, 10 RIC::TeTx transgenic worms, and 10 non-transgenic siblings. (K) Statistical testing for the spontaneous calcium event frequency in AVA of 1-day adult males under different genetic backgrounds for DVC neuron manipulation. 10 wild-type worms, 13 DVC::TeTx transgenic worms, and 13 non-transgenic siblings. (L) Statistical testing for the spontaneous calcium event frequency in AVA of 1-day adult hermaphrodites under different genetic backgrounds for DVC neuron manipulation. 8 wild-type worms, 11 DVC::TeTx transgenic worms, and 11 non-transgenic siblings. (M) Statistical testing for the spontaneous calcium event frequency in AVA of 1-day adult males under different genetic backgrounds for PQR neuron manipulation. 11 wild-type worms, 14 PQR::TeTx transgenic worms, and 8 non-transgenic siblings. (N) Statistical testing for the spontaneous calcium event frequency in AVA of 1-day adult hermaphrodites under different genetic backgrounds for PQR neuron manipulation. Eight wild-type worms, eight PQR::TeTx transgenic worms, and eight non-transgenic siblings. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 6—figure supplement 1
Chemical synapse number difference of AVA with downstream neurons between male and hermaphrodite.
Figure 6—figure supplement 2
The expression of mCherry linked with TeTx indicates the expression of TeTx protein.
(A) RIC neuron; (B) DVC neuron; (C) PQR neuron.
Figure 6—figure supplement 3
Reversal rates from an independent PQR::TeTx strain PSC229 indicate PQR is not involved in male’s enhanced local search behavior.
Sample size: 22 wild-type worms, 23 transgenic worms, and 17 non-transgenic siblings in males.
Figure 7 with 1 supplement
Receptors in AVA that are responsible for the increased local search in males.
(A) Summary of receptor examined in this study. (B) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for glr-2 manipulation in AVA. 22 wild-type worms, 22 AVA::glr-2 RNAi transgenic worms, and 21 non-transgenic siblings. (C) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for glr-2 manipulation in AVA. 18 wild-type worms, 20 AVA::glr-2 RNAi transgenic worms, and 20 non-transgenic siblings. (D) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for nmr-1 manipulation in AVA. 20 wild-type worms, 19 AVA::nmr-1 RNAi transgenic worms, and 18 non-transgenic siblings. (E) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for nmr-1 manipulation in AVA. 24 wild-type worms, 20 AVA::nmr-1 RNAi transgenic worms, and 18 non-transgenic siblings. (F) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for nmr-2 manipulation in AVA. 19 wild-type worms, 19 AVA::nmr-2 RNAi transgenic worms, and 19 non-transgenic siblings. (G) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for nmr-1 manipulation in AVA. 20 wild-type worms, 20 AVA::nmr-2 RNAi transgenic worms, and 20 non-transgenic siblings. (H) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for ser-3 manipulation in AVA. 22 wild-type worms, 21 AVA::ser-3 RNAi transgenic worms, and 20 non-transgenic siblings. (I) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for ser-3 manipulation in AVA. 16 wild-type worms, 17 AVA::ser-3 RNAi transgenic worms, and 16 non-transgenic siblings. (J) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult males under different genetic backgrounds for ser-6 manipulation in AVA. 21 wild-type worms, 19 AVA::ser-6 RNAi transgenic worms, and 20 non-transgenic siblings. (K) Statistical testing for the average reversal rate between minutes 7–10 of 1-day adult hermaphrodites under different genetic backgrounds for ser-6 manipulation in AVA. 17 wild-type worms, 18 AVA::ser-6 RNAi transgenic worms, and 16 non-transgenic siblings. Student’s t-test for all the statistical tests. *p<0.05, **p<0.01, ***p≤0.001.
Figure 7—figure supplement 1
Chemical synapse number difference of AVA with downstream neurons between male (A) and hermaphrodite (B).
Sample size: 20 wild-type worms, 20 transgenic worms, and 19 non-transgenic siblings in males and 14 wild-type worms, 18 transgenic worms, and 19 non-transgenic siblings in hermaphrodites.
Additional files
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MDAR checklist
- https://cdn.elifesciences.org/articles/102309/elife-102309-mdarchecklist1-v1.docx
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Supplementary file 1
The neural connection network of Caenorhabditis elegans.
- https://cdn.elifesciences.org/articles/102309/elife-102309-supp1-v1.xlsx
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Supplementary file 2
The functional classification of neurons with strong synaptic connections.
- https://cdn.elifesciences.org/articles/102309/elife-102309-supp2-v1.xlsx
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Supplementary file 3
Sex-specific synaptic connections.
- https://cdn.elifesciences.org/articles/102309/elife-102309-supp3-v1.xlsx
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Supplementary file 4
The most strongly correlated neuronal pairs in the stimulation simulation.
- https://cdn.elifesciences.org/articles/102309/elife-102309-supp4-v1.xlsx
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Supplementary file 5
The plasmids and reaction primers used in this study.
- https://cdn.elifesciences.org/articles/102309/elife-102309-supp5-v1.xlsx
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Source code 1
Neurodynamic simulation code.
- https://cdn.elifesciences.org/articles/102309/elife-102309-code1-v1.zip
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Dimorphic neural network architecture prioritizes sexual-related behaviors in male Caenorhabditis elegans
eLife 14:RP102309.
https://doi.org/10.7554/eLife.102309.2
