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Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

Li Y, Zhao Y, Huang X, Lin X, Guo Y, Wang D, Li C, Wang D - PLoS ONE (2013)

Bottom Line: Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory.Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants.Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.

ABSTRACT
Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

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Thermotaxis memory behavior of mutants for genes required for serotonin synthesis.(A) Thermotaxis memory assay model [7]. (B) Extinction of the association (food at 20°C) of mutant animals. The normalized isothermal tracking behavior (IT) values were used. (C) Comparison of the extinctions of wild-type and mutant animals at the time interval of 18-hr. (D) Thermotaxis behavior of wild-type and mutant animals. In the thermotaxis assay system, movement to 25°C was scored as thermophilic (T); movement to 17°C was scored as cryophilic (C); movement across the thermal gradient (17°C/25°C) was scored as athermotactic (A); and movement at 20°C was scored as IT. (E–F) Genetic interaction of tph-1 with bas-1 in regulating thermotaxis memory. Bars represent means ± S.E.M. **p<0.01.
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pone-0077779-g001: Thermotaxis memory behavior of mutants for genes required for serotonin synthesis.(A) Thermotaxis memory assay model [7]. (B) Extinction of the association (food at 20°C) of mutant animals. The normalized isothermal tracking behavior (IT) values were used. (C) Comparison of the extinctions of wild-type and mutant animals at the time interval of 18-hr. (D) Thermotaxis behavior of wild-type and mutant animals. In the thermotaxis assay system, movement to 25°C was scored as thermophilic (T); movement to 17°C was scored as cryophilic (C); movement across the thermal gradient (17°C/25°C) was scored as athermotactic (A); and movement at 20°C was scored as IT. (E–F) Genetic interaction of tph-1 with bas-1 in regulating thermotaxis memory. Bars represent means ± S.E.M. **p<0.01.

Mentions: In C. elegans, mutations of tph-1 or bas-1 cause deficits in serotonin synthesis [12]–[13]. We first employed the thermotaxis memory assay model (Fig. 1A) to investigate the memory behaviors in tph-1 and bas-1 mutants. Because nematodes tend to migrate toward their cultivation temperature after conditioning (food at 20°C) and move along this isotherm on a radical temperature gradient, the assay model is used to assess a form of memory for thermosensation (Fig. 1A). In this thermotaxis memory assay model, mutations of tph-1 and bas-1 genes shortened the extinction period of the association paradigm (food at 20°C) for different time intervals compared with wild-type N2 nematodes (Fig. 1B). In addition, mutation of cat-4 gene, involved in control of TPH-1 activity [13], also decreased memory behavior compared with wild-type N2 nematodes (Fig. 1B). In the assay model, the percentages of animals performing isothermal tracking behavior (IT) at the time interval of 18-hr were significantly decreased in tph-1(mg280), bas-1(ad446), and cat-4(e1141) mutants compared with wild-type N2 (Fig. 1C). Compared with the phenotype that wild-type N2 needs 3-hr to perform the half maximal extinction, tph-1(mg280) and bas-1(ad446) mutants used approximately 1-hr and cat-4(e1141) mutants used approximately 2-hr to finish the half maximal extinction (Fig. 1B). To ensure that the altered thermotaxis memory behaviors in tph-1, bas-1, and cat-4 mutants were not due to the deficits in thermotaxis behavior, we examined the thermotaxis behaviors in tph-1(mg280), bas-1(ad446), and cat-4(e1141) mutants. Our data showed that tph-1(mg280), bas-1(ad446), and cat-4(e1141) mutants exhibited the similar thermotaxis phenotype to that of wild-type N2 (Fig. 1D). These data demonstrate that genes required for serotonin synthesis are essential for thermotaxis memory control in C. elegans. Our results also imply the possible important role of neurotransmitter of serotonin in thermotaxis memory control.


Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

Li Y, Zhao Y, Huang X, Lin X, Guo Y, Wang D, Li C, Wang D - PLoS ONE (2013)

Thermotaxis memory behavior of mutants for genes required for serotonin synthesis.(A) Thermotaxis memory assay model [7]. (B) Extinction of the association (food at 20°C) of mutant animals. The normalized isothermal tracking behavior (IT) values were used. (C) Comparison of the extinctions of wild-type and mutant animals at the time interval of 18-hr. (D) Thermotaxis behavior of wild-type and mutant animals. In the thermotaxis assay system, movement to 25°C was scored as thermophilic (T); movement to 17°C was scored as cryophilic (C); movement across the thermal gradient (17°C/25°C) was scored as athermotactic (A); and movement at 20°C was scored as IT. (E–F) Genetic interaction of tph-1 with bas-1 in regulating thermotaxis memory. Bars represent means ± S.E.M. **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3815336&req=5

pone-0077779-g001: Thermotaxis memory behavior of mutants for genes required for serotonin synthesis.(A) Thermotaxis memory assay model [7]. (B) Extinction of the association (food at 20°C) of mutant animals. The normalized isothermal tracking behavior (IT) values were used. (C) Comparison of the extinctions of wild-type and mutant animals at the time interval of 18-hr. (D) Thermotaxis behavior of wild-type and mutant animals. In the thermotaxis assay system, movement to 25°C was scored as thermophilic (T); movement to 17°C was scored as cryophilic (C); movement across the thermal gradient (17°C/25°C) was scored as athermotactic (A); and movement at 20°C was scored as IT. (E–F) Genetic interaction of tph-1 with bas-1 in regulating thermotaxis memory. Bars represent means ± S.E.M. **p<0.01.
Mentions: In C. elegans, mutations of tph-1 or bas-1 cause deficits in serotonin synthesis [12]–[13]. We first employed the thermotaxis memory assay model (Fig. 1A) to investigate the memory behaviors in tph-1 and bas-1 mutants. Because nematodes tend to migrate toward their cultivation temperature after conditioning (food at 20°C) and move along this isotherm on a radical temperature gradient, the assay model is used to assess a form of memory for thermosensation (Fig. 1A). In this thermotaxis memory assay model, mutations of tph-1 and bas-1 genes shortened the extinction period of the association paradigm (food at 20°C) for different time intervals compared with wild-type N2 nematodes (Fig. 1B). In addition, mutation of cat-4 gene, involved in control of TPH-1 activity [13], also decreased memory behavior compared with wild-type N2 nematodes (Fig. 1B). In the assay model, the percentages of animals performing isothermal tracking behavior (IT) at the time interval of 18-hr were significantly decreased in tph-1(mg280), bas-1(ad446), and cat-4(e1141) mutants compared with wild-type N2 (Fig. 1C). Compared with the phenotype that wild-type N2 needs 3-hr to perform the half maximal extinction, tph-1(mg280) and bas-1(ad446) mutants used approximately 1-hr and cat-4(e1141) mutants used approximately 2-hr to finish the half maximal extinction (Fig. 1B). To ensure that the altered thermotaxis memory behaviors in tph-1, bas-1, and cat-4 mutants were not due to the deficits in thermotaxis behavior, we examined the thermotaxis behaviors in tph-1(mg280), bas-1(ad446), and cat-4(e1141) mutants. Our data showed that tph-1(mg280), bas-1(ad446), and cat-4(e1141) mutants exhibited the similar thermotaxis phenotype to that of wild-type N2 (Fig. 1D). These data demonstrate that genes required for serotonin synthesis are essential for thermotaxis memory control in C. elegans. Our results also imply the possible important role of neurotransmitter of serotonin in thermotaxis memory control.

Bottom Line: Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory.Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants.Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China.

ABSTRACT
Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

Show MeSH