Aging-Dependent and -Independent Modulation of Associative Learning Behavior by Insulin/Insulin-Like Growth Factor-1 Signal in<i>Caenorhabditis elegans</i>

Murakami, Hana; Bessinger, Karalee; Hellmann, Jason; Murakami, Shin

doi:10.1523/jneurosci.3600-04.2005

Cited by 114 publications

(97 citation statements)

References 58 publications

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“…This is consistent with at least some perception of food in daf-2 mutants. Moreover, mutations in daf-2 and age-1 were shown recently to influence behavioral plasticity of temperature-induced responses (Murakami et al 2005), supporting the role of insulin/IGF-1 signaling in learning per se.…”

Section: Resultsmentioning

confidence: 83%

“…Furthermore, mutations in the PTEN phosphatase daf-18, which increase insulin/IGF-1 signaling, result in an enhancement of learning ability. The role of the insulin/IGF-1 signaling cascade in nematode learning is further supported by a recent study of insulin/IGF-1 signaling pathway mutants, which demonstrated their influence on behavioral plasticity in response to changing temperature (Murakami et al 2005).…”

Section: Discussionmentioning

confidence: 84%

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Effects of Sex and Insulin/Insulin-Like Growth Factor-1 Signaling on Performance in an Associative Learning Paradigm inCaenorhabditis elegans

Vellai¹,

McCulloch

Gems

et al. 2006

Genetics

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Learning is an adaptive change in behavior in response to environmental stimuli. In mammals, there is a distinct female bias to learn skills that is still unprecedented in other animal taxa. Here we have investigated the biological determinants of performance in an associative learning paradigm in the nematode Caenorhabditis elegans. Using an assay of chemotactic reactions associated with food deprivation, wild-type male worms show inferior learning ability relative to hermaphrodites. Sex-based learning difference is therefore an ancient evolutionary feature appearing even in relatively simple animals. C. elegans mutants with reduced insulin/IGF-1 signaling also exhibit a greatly reduced learning ability in this assay. In addition, hyperactivation of insulin/IGF-1 signaling through loss-of-function mutations in the PTEN phosphatase daf-18, a negative regulator of insulin/IGF-1 signaling, enhances learning ability beyond that of wild type. According to our epistasis analysis, the effect of DAF-2 on learning acts via phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) production, but not the DAF-16 FOXO transcription factor. This implies that the signaling pathway from DAF-2 affecting this learning paradigm branches between PIP 3 production and DAF-16. However, learning capacity of nematodes is lowered by loss-offunction mutations in daf-16, suggesting involvement of noninsulin/IGF-1 signaling-dependent DAF-16 activation in learning. Potentially, sex and insulin/IGF-1 signaling affect performance in this learning assay via effects on the neurobiology of learning.

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Section: Resultsmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 84%

Effects of Sex and Insulin/Insulin-Like Growth Factor-1 Signaling on Performance in an Associative Learning Paradigm inCaenorhabditis elegans

Vellai¹,

McCulloch

Gems

et al. 2006

Genetics

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“…The method of head thrash frequency, body bend frequency, and basic movements were performed as previously described (Tsalik and Hobert, 2003;Murakami et al, 2005). To assay the head thrashes, young adult nematodes were washed with double-distilled water, followed by washing with M9 medium.…”

Section: Behavioral Analysismentioning

confidence: 99%

Intracellular Trafficking of Histone Deacetylase 4 Regulates Long‐Term Memory Formation

Wang

Cheng

Pan

et al. 2011

The Anatomical Record

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Histone acetylation is important for gene transcription, which is controlled by the balance between two kinds of opposing enzymes: histone acetyltransferases and histone deacetylases (HDACs). HDACs repress gene transcription by decreasing histone acetylation levels. Our hypothesis was that shuttling of Class II HDACs, such as HDAC4, between the nucleus and cytoplasm is critical for its function. We constructed mutants of mammalian HDAC4 that had different cellular locations and checked their function during memory formation using Caenorhabditis elegans as a model. The deletion of hda4, a homolog of HDAC4, was able to enhance learning and long-term memory (LTM) in a thermotaxis model. Transgenic experiments showed that mammalian wild-type HDAC4 rescued the phenotype of hda4-deleted worms but impaired LTM formation in wild-type worms. The cytosol-localized HDAC4 mutant was not able to alter the phenotype of knock-out worms but led to enhanced LTM formation in wild-type worms similar to hda4-deletion mutants. Constitutive nuclear localization of HDAC4 rescued the phenotype of deletion worms similar to wild-type HDAC4 but had no effect on wild-type worms. These results support our hypothesis that HDAC4's biological function is regulated by its intracellular distribution. Anat Rec, 294:1025Rec, 294: -1034Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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“…Previous studies have identified the neural circuit and several genes required for thermotaxis (Mori and Ohshima 1995;Komatsu et al 1996;Ishihara et al 2002;Kuhara et al 2002;Murakami et al 2005;Okochi et al 2005;Inada et al 2006). However, how C. elegans executes thermotaxis remains to be understood at the molecular and physiological levels.…”

Section: Insulin Homolog Ins-1 Is Required For Food-associated Tempermentioning

confidence: 99%

Insulin-like signaling and the neural circuit for integrative behavior in C. elegans

Kodama¹,

Kuhara²,

et al. 2006

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Caenorhabditis elegans exhibits a food-associated behavior that is modulated by the past cultivation temperature. Mutations in INS-1, the homolog of human insulin, caused the defect in this integrative behavior. Mutations in DAF-2/insulin receptor and AGE-1/phosphatidylinositol 3 (PI-3)-kinase partially suppressed the defect of ins-1 mutants, and a mutation in DAF-16, a forkhead-type transcriptional factor, caused a weak defect. In addition, mutations in the secretory protein HEN-1 showed synergistic effects with INS-1. Expression of AGE-1 in any of the three interneurons, AIY, AIZ, or RIA, rescued the defect characteristic of age-1 mutants. Calcium imaging revealed that starvation induced INS-1-mediated down-regulation of AIZ activity. Our results suggest that INS-1, in cooperation with HEN-1, antagonizes the DAF-2 insulin-like signaling pathway to modulate interneuron activity required for food-associated integrative behavior. The secreted peptide hormone insulin modulates neural plasticity. Insulin and insulin receptors are expressed in several regions of the rat brain (Havrankova et al. 1978a,b), insulin receptors localize to post-synapses (Abbott et al. 1999), and insulin can produce long-term depression (LTD) of synaptic transmission through endocytosis of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rat hippocampal CA1 neurons (Man et al. 2000). In addition, Phosphatidylinositol 3 (PI-3)-kinase that functions in the insulin signaling pathway is thought to induce long-term potentiation (LTP) of synaptic transmission in the dentate gyrus of rat (Kelly and Lynch 2000). These alterations by proteins of the insulin signaling pathway may be involved in learning and memory, but what kind of behavior the insulin signaling pathway modulates has been largely unknown.The nematode Caenorhabditis elegans is well suited for the analysis of the molecular and cellular mechanisms underlying neural plasticity because of its accessible genetics, stereotyped behavioral responses, and its simple nervous system consisting of 302 neurons whose connections are entirely known (White et al. 1986). Recently, physiological analysis of the neural circuit in live worms has become possible by the use of cameleon, a genetically encodable calcium indicator, to measure Ca 2+ concentration changes (Miyawaki et al. 1997;Kimura et al. 2004).C. elegans exhibits thermotaxis, an integrative behavior in which well-fed animals in a thermal gradient are attracted to their cultivation temperature, whereas starved animals avoid it (Hedgecock and Russell 1975;Mohri et al. 2005;Rankin 2005). This food-associated behavioral plasticity, regarded the most complex behavior in C. elegans, is an ideal behavioral paradigm for comprehensive study of neural plasticity at the molecular, physiological, and behavioral levels. In this study, we show that in cooperation with a secreted protein HEN-1, an insulin homolog INS-1, and insulin-like signaling pathway modulate neuronal activity of interneurons to execute thermotaxis behavior in...

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Aging-Dependent and -Independent Modulation of Associative Learning Behavior by Insulin/Insulin-Like Growth Factor-1 Signal inCaenorhabditis elegans

Cited by 114 publications

References 58 publications

Effects of Sex and Insulin/Insulin-Like Growth Factor-1 Signaling on Performance in an Associative Learning Paradigm inCaenorhabditis elegans

Effects of Sex and Insulin/Insulin-Like Growth Factor-1 Signaling on Performance in an Associative Learning Paradigm inCaenorhabditis elegans

Intracellular Trafficking of Histone Deacetylase 4 Regulates Long‐Term Memory Formation

Insulin-like signaling and the neural circuit for integrative behavior in C. elegans

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