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A gene-expression-based neural code for food abundance that modulates lifespan.

Entchev EV, Patel DS, Zhan M, Steele AJ, Lu H, Ch'ng Q - Elife (2015)

Bottom Line: These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses.This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan.Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

ABSTRACT
How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGFβ and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

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Food encoding accuracy of all neuron combinations and lifespan outputs for wildtype and mutant animals.(A, C, E, G) Matrices of probability-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wildtype and mutant animals. These results are based on distributing the calculated raw probabilities of animals being from each food condition before assigning animals to particular food levels based on maximum likelihood. (B, D, F, H) Matrices of maximum likelihood-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wild type and mutant animals. Genotype is denoted by the colored borders around the matrices and indicated in the legend below (A and B).DOI:http://dx.doi.org/10.7554/eLife.06259.016
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fig6s1: Food encoding accuracy of all neuron combinations and lifespan outputs for wildtype and mutant animals.(A, C, E, G) Matrices of probability-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wildtype and mutant animals. These results are based on distributing the calculated raw probabilities of animals being from each food condition before assigning animals to particular food levels based on maximum likelihood. (B, D, F, H) Matrices of maximum likelihood-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wild type and mutant animals. Genotype is denoted by the colored borders around the matrices and indicated in the legend below (A and B).DOI:http://dx.doi.org/10.7554/eLife.06259.016

Mentions: To understand the multifaceted effects of daf-7 and tph-1 signalling on fidelity, we computed the encoding accuracy of neuronal gene expression in daf-7(−) and tph-1(−) mutants using the same maximum likelihood framework as applied to the wildtype animals (Figure 4C,D, and Figure 6—figure supplement 1). tph-1(−) mutants showed increased encoding capability in all readouts while daf-7(−) mutants demonstrated consistently diminished fidelity (Figure 6A), consistent with their respective effects on dynamic range and the variability of gene expression (Figure 5B,D). The intermediate encoding capability of the double mutants reflects the additive effects of the mutations with regard to encoding (Figures 5B,C, 6A). As with wildtype animals, combining information from multiple neurons tended to increase the accuracy in these mutants and tph-1 expression in the NSM and ADF neurons accounted for the majority of this representational capability (Figure 6B). These results showed that tph-1 and daf-7 served mechanistically distinct and opposing roles in modulating the fidelity of this food representation (Figure 6C,D). Whilst the transcriptional responses of daf-7 itself added little encoding capability overall (Figures 4D, 6B), its regulatory role in reducing gene-expression variability facilitated the encoding power of tph-1 (Figure 6B,C). Conversely, tph-1 outputs served a major encoding role in the system (Figure 6B), but its regulatory effect decreased the dynamic range of transcriptional responses (Figure 5B) and limited the encoding accuracy of the system in wildtype animals (Figure 6C). Together, our results reveal the roles of cross- and self-regulation within this circuit, and the mechanisms by which tph-1 and daf-7 tune performance.10.7554/eLife.06259.015Figure 6.Cross- and self-regulation of tph-1 and daf-7 control the accuracy of internal representation of food levels.


A gene-expression-based neural code for food abundance that modulates lifespan.

Entchev EV, Patel DS, Zhan M, Steele AJ, Lu H, Ch'ng Q - Elife (2015)

Food encoding accuracy of all neuron combinations and lifespan outputs for wildtype and mutant animals.(A, C, E, G) Matrices of probability-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wildtype and mutant animals. These results are based on distributing the calculated raw probabilities of animals being from each food condition before assigning animals to particular food levels based on maximum likelihood. (B, D, F, H) Matrices of maximum likelihood-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wild type and mutant animals. Genotype is denoted by the colored borders around the matrices and indicated in the legend below (A and B).DOI:http://dx.doi.org/10.7554/eLife.06259.016
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417936&req=5

fig6s1: Food encoding accuracy of all neuron combinations and lifespan outputs for wildtype and mutant animals.(A, C, E, G) Matrices of probability-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wildtype and mutant animals. These results are based on distributing the calculated raw probabilities of animals being from each food condition before assigning animals to particular food levels based on maximum likelihood. (B, D, F, H) Matrices of maximum likelihood-based food encoding fidelity for single and combined neuronal outputs and lifespan outputs in the wild type and mutant animals. Genotype is denoted by the colored borders around the matrices and indicated in the legend below (A and B).DOI:http://dx.doi.org/10.7554/eLife.06259.016
Mentions: To understand the multifaceted effects of daf-7 and tph-1 signalling on fidelity, we computed the encoding accuracy of neuronal gene expression in daf-7(−) and tph-1(−) mutants using the same maximum likelihood framework as applied to the wildtype animals (Figure 4C,D, and Figure 6—figure supplement 1). tph-1(−) mutants showed increased encoding capability in all readouts while daf-7(−) mutants demonstrated consistently diminished fidelity (Figure 6A), consistent with their respective effects on dynamic range and the variability of gene expression (Figure 5B,D). The intermediate encoding capability of the double mutants reflects the additive effects of the mutations with regard to encoding (Figures 5B,C, 6A). As with wildtype animals, combining information from multiple neurons tended to increase the accuracy in these mutants and tph-1 expression in the NSM and ADF neurons accounted for the majority of this representational capability (Figure 6B). These results showed that tph-1 and daf-7 served mechanistically distinct and opposing roles in modulating the fidelity of this food representation (Figure 6C,D). Whilst the transcriptional responses of daf-7 itself added little encoding capability overall (Figures 4D, 6B), its regulatory role in reducing gene-expression variability facilitated the encoding power of tph-1 (Figure 6B,C). Conversely, tph-1 outputs served a major encoding role in the system (Figure 6B), but its regulatory effect decreased the dynamic range of transcriptional responses (Figure 5B) and limited the encoding accuracy of the system in wildtype animals (Figure 6C). Together, our results reveal the roles of cross- and self-regulation within this circuit, and the mechanisms by which tph-1 and daf-7 tune performance.10.7554/eLife.06259.015Figure 6.Cross- and self-regulation of tph-1 and daf-7 control the accuracy of internal representation of food levels.

Bottom Line: These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses.This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan.Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

ABSTRACT
How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGFβ and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

Show MeSH
Related in: MedlinePlus