Wat je van wormen leren kan
Stelt u zich even voor dat u op een maandagnamiddag aan het werk bent. De deur van de kamer gaat open en iemand komt u koffie brengen. Wellicht herkent u het gevoel dat u zich wakkerder begint te voelen nog voor u een slok koffie heeft gedronken.
U had het misschien niet gedacht, maar zo’n mechanisme van Pavloviaanse conditionering waarbij u leerde de geur van koffie te onthouden om die te associëren met hoe u zich later zult voelen, is evolutionair gezien erg oud. Het vermogen om te leren uit ervaringen is voor mens en dier namelijk essentieel om zich aan te passen aan een voortdurend veranderende omgeving. Zo laat het toe verbanden te leren onthouden tussen hoe u zich nu voelt en wat daaraan vooraf is gegaan.
Anderhalve eeuw lang zochten wetenschappers naar antwoorden op de vraag hoe de hersenen herinneringen kunnen vormen en vasthouden. Ondanks globale inspanningen, blijven we echter nog grotendeels in het ongewisse wat betreft de fundamentele mechanismen die herinneringen vorm geven.
C. elegans (© Sara Van Damme)
Man is but a worm
Lang werd gedacht dat leren en het vormen van geheugen een louter menselijk kenmerk was. Nu weten we dat het zenuwstelsel van de meeste, zo niet van alle dieren in staat is herinneringen te vormen en op te slaan. Zo ook dat van een microscopisch kleine rondworm.
Deze rondworm, Caenorhabditis elegans, is bijzonder geschikt om fundamentele processen zoals leergedrag te bestuderen. In vergelijking met de miljard zenuwcellen die het menselijk brein telt, heeft deze nematode er slechts 302, niet meer en niet minder. Niettemin kan ook deze rondworm associaties leren en gebeurt dit zeer gelijkaardig als bij andere dieren. Hierdoor kunnen we processen die bijdragen aan het vormen van geheugen bestuderen in een minder complex zenuwstelsel.
Bovendien is de exacte positie van elk van die 302 zenuwcellen in kaart gebracht, inclusief alle verbindingen die ze maken met naburige zenuwcellen. Met die kennis kunnen wetenschappers voorspellingen maken over de rol van individuele cellen in het leerproces. Onderzoek naar de onderliggende mechanismen wordt nog verder vergemakkelijkt doordat deze rondworm doorzichtig is. Door cellen en signaalstoffen fluorescent te maken, kunnen we kijken naar hun werking in levende wormen zonder te moeten dissecteren.
Computermodel van de 302 neuronen van de rondworm (OpenWorm Project)
Een receptoreiwit met een geurtje aan
Chemische signalen, zoals hormonen, sturen de werking van het zenuwstelsel om gedrag aan te passen aan de actuele noden van een dier. Chemische moleculen vervullen die rol door te binden aan receptoreiwitten op het oppervlak van zenuwcellen. Op dezelfde manier zijn signaal-receptorkoppels ook betrokken bij de overdracht van informatie in het leerproces. Ik bestudeerde zo’n receptoreiwit dat voorkomt in het zenuwstelsel van C. elegans, waarvan de naam wordt afgekort als NPR-6. Welke processen dit receptoreiwit precies beïnvloedt, was voorlopig onduidelijk en probeerde ik beter te begrijpen.
Omdat de vorm van een eiwit ons veel kan leren over de functie ervan, zochten we eerst in online databases naar gelijkaardige eiwitten uit andere dieren. Tijdens deze zoektocht botste ik op een zeer gelijkaardig receptoreiwit in insecten, waarvan we weten dat het hun leergedrag beïnvloedt. Om te onderzoeken of dit ook zo is bij rondwormen, testte ik het leervermogen van
mutante wormen waarin dit receptoreiwit niet meer werkzaam is.
In leertesten leren wormen een negatieve associatie tussen voedsel en de geurstof.
Wormen met een functionele kopie van het receptoreiwit zijn uit zichzelf aangetrokken tot de geurstof diacetyl. Na de wormen echter drie uur lang bloot te stellen aan deze geur in de afwezigheid van voedsel, leren ze dat deze geur niets goeds betekent en zullen ze die geur in de toekomst vermijden. In initiële experimenten ontdekte ik dat mutante wormen die het receptoreiwit missen, moeite hebben om deze associatie te maken. Bijgevolg lijkt het receptoreiwit ook in rondwormen leergedrag te sturen.
Om te onderzoeken waar precies in het leerproces deze receptor een rol speelt, probeerde ik vervolgens uit te vinden op welke cellen het receptoreiwit aanwezig is. Om dit te ontdekken, koppelde ik in het DNA van de wormen een fluorescent eiwit aan ons receptoreiwit. Als resultaat lichten alle cellen waarin het receptoreiwit aanwezig is groen op. Zoals de geobserveerde leerdefecten deden voorspellen, ontdekte ik dat het eiwit voorkomt in die cellen waarvan we reeds weten dat ze leergedrag sturen.
Fluorescente zenuwcellen in het hoofd van de worm
Tot mijn verbazing waren dit niet de enige cellen die groen oplichtten: het receptoreiwit komt ook voor op cellen die gekend zijn voor hun rol in het sturen van het bewegingspatroon van de wormen. Als er eten in de buurt is, bewegen wormen trager en kruipen ze niet ver weg. Wanneer ze daarentegen honger krijgen, gaan ze op zoek naar betere oorden. Een gedetailleerde analyse van de bewegingen die wormen maken, bevestigde dat mutante wormen zich inderdaad anders gedragen dan wormen met een functionele kopie van het receptoreiwit. Zo lijken mutante wormen steeds honger te hebben, gezien ze vastbesloten op zoek gaan naar betere oorden, zelfs in de aanwezigheid van hun favoriete voedsel.
Tot slot zocht ik naar chemische signalen die de informatie overbrengen via dit receptoreiwit. Dit deed ik door stamcellen het eiwit te laten aanmaken. Wanneer een signaalmolecule bindt aan de receptor op deze stamcellen, lichten deze cellen op. Zo ontdekte ik twaalf mogelijke signaalmoleculen voor dit receptoreiwit. In lijn met mijn voorgaande observaties, werd in de literatuur reeds voor tien van die moleculen een rol gerapporteerd in voedsel-gerelateerd gedrag.
Waarom we geven om het eetgedrag van wormen
Waarom ik zo enthousiast ben door deze bevindingen? Hongersignalen en de associatie van zulke gevoelens met geuren zetten niet alleen agrarische pestsoorten, maar ook parasitaire rondwormen en ziekte-overdragende insecten ertoe aan om hun gastheer, zij het landbouwgewassen of mens en dier, te infecteren. Doordat dit receptoreiwit enkel voorkomt in ongewervelde dieren is het een ideaal doelwit voor de ontwikkeling van duurzame en veilige biologische bestrijdingsmiddelen. Zo dragen verbeterde inzichten in de onderliggende mechanismen van leergedrag en voedsel-afhankelijke gedragingen bij tot de zoektocht om landbouwopbrengsten te vergroten en parasitaire infecties te bestrijden.
Bibliografie
WormBase: www.wormbase.org
FlyBase: www.flybase.org
NCBI: www.ncbi.nlm.nih.gov
Albertson, D.G. and Thomson J.N. 1975. “The Pharynx of Caenorhabditis elegans.” Proceedings. Biological sciences / The Royal Society 308: 299–325.
Alcock, J. 2012. Animal Behaviour: An Evolutionary Approach. 10th ed. Sunderlands: Sinauer Associates.
Altschul, S.F. et al. 1990. “Basic Local Alignment Search Tool.” Journal of Molecular Biology 215(3): 403–10.
Altschul, S.F. et al. 1997. “Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs.” Nucleic Acids Research 25(17): 3389–3402.
Altun, Z.F. and Hall D.H. . 2005. “Cell Identification in C. elegans.” In WormAtlas, http://www.wormatlas.org/cellID.html.
Ament, S A et al. 2011. “Neuropeptide Y-like Signalling and Nutritionally Mediated Gene Expression and Behaviour in the Honey Bee.” Insect Molecular Biology 20(3): 335–45.
Ardiel, E.L. et al. 2016. “Dopamine Receptor DOP-4 Modulates Habituation to Repetitive Photoactivation of a C. elegans Polymodal Nociceptor.” Learning & memory 23: 495–503.
Ardiel, E.L. and Rankin, C.H. 2010. “An Elegant Mind: Learning and Memory in Caenorhabditis elegans.” Learning & memory 17(4): 191–201.
Avery, L. and Horvitz, H.R. 1990. “Effects of Starvation and Neuroactive Drugs on Feeding in Caenorhabditis elegans.” Journal of Experimental Zoology 253: 263–70.
Avery, L. and Horvitz, H.R. 1989. “Pharyngeal Pumping Continues after Laser Killing of the Pharyngeal Nervous System of C. elegans.” Neuron 3(1981): 473–85.
Ayachi, S. and Simonin, F. 2014. “Involvement of Mammalian RF-Amide Peptides and Their Receptors in the Modulation of Nociception in Rodents.” Frontiers in Endocrinology 5(October): 1–13.
Bacaj, T., Maya T., Yun L., and Shaham, S. 2008. “Glia Are Essential for Sensory Organ Function in C. elegans.” Science 322(October): 744–48.
Van Bael, S. et al. 2018. “Mass Spectrometric Evidence for Neuropeptide-Amidating Enzymes in Caenorhabditis elegans.” Journal of Biological Chemistry 293(16).
Bao, C., Yanan Y., Huiyang H., and Ye, H. 2018. “Inhibitory Role of the Mud Crab Short Neuropeptide F in Vitellogenesis and Oocyte Maturation via Autocrine/Paracrine Signaling.” Frontiers in Endocrinology 9(July): 1–11.
Bargmann, C.I. 2012. “Beyond the Connectome: How Neuromodulators Shape Neural Circuits.” Bioessays 34(1): 458–65.
Bargmann, C.I., Hartwieg, E., and Horvitz, R.H. 1993. “Odorant-Selective Genes and Neurons Mediate Olfaction in C. elegans.” Cell 74(August): 515–27.
Bargmann, C.I., and Horvitz, R.H. 1991. “Chemosensory Neurons with Overlapping Direct Chemotaxis to Multiple Chemicals in C. elegans” Neuron 7(November): 729–42.
Barnstedt, O. et al. 2016. “Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.” Neuron 89(6): 1237–47. http://dx.doi.org/10.1016/j.neuron.2016.02.015.
Batterham, R.L. et al. 2002. “Gut Hormone
PYY3-36 Physiologically Inhibits Food Intake.” Nature 418(August): 728–30.
Bear, M.F., Connors, B.W., and Paradiso, M.A. 2016. Neuroscience: Exploring the Brain. 4th ed. Philadelphia: Wolters Kluwers.
Beets, I. et al. 2012. “Associative Learning in C. elegans.” Science 338(October): 543–46.
Beets, I., Lindemans, M., Janssen, T. and Verleyen, P.. 2011. “Deorphanizing G Protein-Coupled Receptors by a Calcium Mobilization Assay.” In Neuropeptides, ed. Merighi, A. New York: Springer Science+Business Media, 416.
Bendesky, A. et al. 2011. “Catecholamine Receptor Polymorphisms Affect Decision-Making in C. elegans.” Nature 472(7343): 313–doi:10.1038/nature09821.
Bentley, B. et al. 2016. “The Multilayer Connectome of Caenorhabditis elegans.” PLoS computational biology 12(12): e1005283. doi:10.1371/ journal.pcbi.1005283
Bernard, G.C., Egnin, M. and Bonsi, B. 2016. “The Impact of Plant-Parasitic Nematodes on Agriculture and Methods of Control.” In Nematology - Concepts, Diagnosis and Control, ed. Shah, M.M. and Mahamood, doi: 10.5772/intechopen.68958123
Bhardwaj, A., Thapliyal, S., Dahiya, Y. and Babu, K. 2018. “FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans.” The Journal of Neuroscience 38(20): 4641–54. http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.1955-17.2018.
Bjursell, M. et al. 2007. “GPR10 Deficiency in Mice Results in Altered Energy Expenditure and Obesity.” Biochemical and Biophysical Research Communications 363(3): 633–38.
Blakemore, L.J., Levenson, C.W. and Trombley, P.Q. 2006. “Neuropeptide Y Modulates Excitatory Synaptic Transmission in the Olfactory Bulb.” Neuroscience 138(2): 663–74.
de Bono, M. et al. 2002. “Social Feeding in Caenorhabditis elegans Is Induced by Neurons That Detect Aversive Stimuli.” Nature 419(6910): 899–903.
de Bono, M., and Maricq, A.V. 2005. “Neuronal Substrates of Complex Behaviours in C. elegans.” Annual Review of Neuroscience 28(1): 451–501.
Brenner, S. 1974. “The DNA of Caenorhabditis elegans.” Genetics 77(1): 95–104.
Broberger, C. et al. 1997. “Subtypes Y1 and Y2 of the Neuropeptide Y Receptor Are Respectively Expressed in Pro-Opiomelanocortin- and Neuropeptide-Y-Containing Neurons of the Rat Hypothalamic Arcuate Nucleus.” Neuroendocrinology 66: 393–408.
Bryant, A.S., and Hallem, E.A. 2018. “Terror in the Dirt: Sensory Determinants of Host Seeking in Soil-Transmitted Mammalian-Parasitic Nematodes.” International Journal for Parasitology: Drugs and Drug Resistance 8(3): 496–510. doi: 10.1016/j.ijpddr.2018.10.008.
Van Buskirk, C., and Sternberg, P.W. 2007. “Epidermal Growth Factor Signaling Induces Behavioral Quiescence in Caenorhabditis elegans.” Nature neuroscience 10(10): 1300–1307.
Caers, J. et al. 2016. “Molecular Characterization of a Short Neuropeptide F Signaling System in the Tsetse Fly, Glossina morsitans morsitans.” General and Comparative Endocrinology 235: 142–49. doi: 10.1016/j.ygcen.2016.06.005.
Calhoun, A.J., Chalasani, S.H. and Sharpee, T.O. 2014. “Maximally Informative Foraging by Caenorhabditis elegans.” eLife 3: 1–13.
Cardoso, J., Rute, C.R., Félix, C., Fonseca, V.G. and Power, D.M. 2012. “Feeding and the Rhodopsin Family G-Protein Coupled Receptors in Nematodes and Arthropods.” Frontiers in Endocrinology 3(December): 1–22.
Carulli, D., Foscarin, S. and Rossi, F. 2011. “Activity-Dependent Plasticity and Gene Expression Modifications in the Adult CNS.” Frontiers in Molecular Neuroscience 4(November): 1–12.
Chao, M.Y. et al. 2004. “Feeding Status and Serotonin Rapidly and Reversibly Modulate a Caenorhabditis elegans Chemosensory Circuit.” PNAS 101(43): 15512–17.
Chen, M., and Patricia, V. 2006. “The Short Neuropeptide F-Like Receptor From the Red Imported Fire Ant, Solenopsis invicta Buren (Hymenoptera : Formicidae).” Archives of Insect Biochemistry and Physiology 208(August): 195–208.
Chen, Z. et al. 2013. “Two Insulin-like Peptides Antagonistically Regulate Aversive Olfactory Learning in C. elegans.” Neuron 77(3): 572–85. doi:10.1016/j.neuron.2012.11.025.
Cheong, M.C., Artyukhin, A.B., You, Y-J. and Avery, L. 2015. “An Opioid-like System Regulating Feeding Behavior in C. elegans.” eLife 4: e06683.
Chevenet, F. et al. 2006. “TreeDyn: Towards Dynamic Graphics and Annotations for Analyses of Trees.” BMC Bioinformatics 7: 1–9.
Choi, S. et al. 2013. “Analysis of NPR-1 Reveals a Circuit Mechanism for Behavioral Quiescence in C. elegans.” Neuron 78(5): 869–80. doi:10.1016/j.neuron.2013.04.002.
Christ, P. et al. 2017. “Feeding-Induced Changes in Allatostatin-A and Short Neuropeptide F in the Antennal Lobes Affect Odor-Mediated Host Seeking in the Yellow Fever Mosquito, Aedes aegypti.” PLoS ONE 12(11): 1–15.
———. 2018. “Functional Characterization of Mosquito Short Neuropeptide F Receptors.” Peptides 103(March): 31–39. doi:10.1016/j.peptides.2018.03.009.
Cohen, M. et al. 2009a. “Coordinated Regulation of Foraging and Metabolism in C. elegans by RFamide Neuropeptide Signaling.” Cell Metabolism 9(4): 375–85. doi:10.1016/j.cmet.2009.02.003.
Colbert, H.A., and Bargmann, C.I. 1997. “Environmental Signals Modulate Olfactory Acuity, Discrimination, and Memory in Caenorhabditis elegans.” Learning and Memory 4(2): 179–91.
Colbert, H.A., and Bargmann, C.I.. 1995. “Odorant-Specific Adaptation Pathways Generate Olfactory Plasticity in C. elegans.” Neuron 14(4): 803–12.
Crocker, A., Guan, X-J., Murphy, C.T. and Murthy, M. 2016. “Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression.” Cell Reports 15(7): 1580–96. doi:10.1016/j.celrep.2016.04.046.
Croll, N.A., and Smith, J.M.. 1978. “Integrated Behaviour in the Feeding Phase of Caenorhabditis elegans (Nematoda).” Journal of Zoology 184(4): 507–17. doi:10.1111/j.1469
Cunningham, K.A. et al. 2012. “AMP-Activated Kinase Links Serotonergic Signaling to Glutamate Release for Regulation of Feeding Behavior in C. elegans.” Cell Metabolism 16(1): 113–21. doi:10.1016/j.cmet.2012.05.014.
Davis, K.C., Choi, Y.I., Kim, J. and You, Y.J. 2018. “Satiety Behavior Is Regulated by ASI/ASH Reciprocal Antagonism.” Scientific Reports 8(1): 3–9. doi:10.1038/s41598-018-24943-6.
Dereeper, A. et al. 2008. “Phylogeny.Fr: Robust Phylogenetic Analysis for the Non-Specialist.” Nucleic acids research 36(July). www.phylogeny.fr.
Dillen, S. et al. 2014. “Identification of the Short Neuropeptide F Precursor in the Desert Locust: Evidence for an Inhibitory Role of sNPF in the Control of Feeding.” Peptides 53: 134–39. doi:10.1016/j.peptides.2013.09.018.
Dong, L. et al. 2014. “Lauric Acid in Crown Daisy Root Exudate Potently Regulates Root-Knot Nematode Chemotaxis and Disrupts Mi-flp-18 Expression to Block Infection.” Journal of Experimental Botany 65(1): 131–41.
Ezcurra, M. et al. 2016. “Neuropeptidergic Signaling and Active Feeding State Inhibit Nociception in Caenorhabditis elegans.” Journal of Neuroscience 36(11): 3157–69. doi:10.1523/JNEUROSCI.1128-15.2016.
Ezcurra, M., Tanizawa, Y., Swoboda, P. and Schafer, W.R.. 2011. “Food Sensitizes C. elegans Avoidance Behaviours through Acute Dopamine Signalling.” The EMBO Journal 30(6): 1110–22. doi:10.1038/emboj.2011.22.
Fadda, M. and Hasakiogullari, I. et al. 2019. “Regulation of Feeding and Metabolism by F in Invertebrates.” Frontiers in Endocrinology 10(February): 1–17.
Farhan, A. et al. 2013. “The CCHamide 1 Receptor Modulates Sensory Perception and Olfactory Behavior in Starved Drosophila.” Scientific Reports 3: 1–6.
Flavell, S.W. et al. 2013. “Serotonin and the Neuropeptide PDF Initiate and Extend Opposing Behavioral States in C. elegans.” Cell 154(5): 1023–35.
Friedlander, Y. et al. 2010. “Candidate Molecular Pathway Genes Related to Appetite Regulatory Neural Network, Adipocyte Homeostasis and Obesity: Results from the CARDIA Study.” Annals of Human Genetics 74(5): 387–98.
Frooninckx, L. et al. 2012. “Neuropeptide GPCRs in C. elegans.” Frontiers in Endocrinology 3(December): 167.
———. 2015. “Novel Gonadotropin-Releasing Hormone, Tachykinin and Neuromedin U Neuropeptide Signaling Systems in Caenorhabditis elegans.” KU Leuven.
Fujiwara, M., Sengupta, P., and McIntire, S.P. 2002. “Regulation of Body Size and Behavioral State of C. elegans by Sensory Perception and the EGL-4 CGMP-Dependent Protein Kinase.” Neuron 36(6): 1091–1102.
Gallagher, T. et al. 2013. “ASI Regulates Satiety Quiescence in C. elegans.” Journal of Neuroscience 33(23): 9716–24.
Garczynski, S.F., Crim, J.W., and Brown, M.R. 2005. “Characterization of Neuropeptide F and Its Receptor from the African Malaria Mosquito, Anopheles gambiae.” Peptides 26(1): 99–107.
Gilbert, S.F., and Barresi, M.J. 2018. “Rapid Specification in Snails and Nematodes.” In Developmental Biology, Oxford: Oxford University Press, 810.
Glauser, D.A. et al. 2011. “Heat Avoidance Is Regulated by Transient Receptor Potential (TRP) Channels and a Neuropeptide Signaling Pathway in Caenorhabditis elegans.” Genetics 188(1): 91–103.
Gøtzsche, C. R., and Woldbye, D.P.D.. 2016. “The Role of NPY in Learning and Memory.” Neuropeptides 55: 79–89. doi:10.1016/j.npep.2015.09.010.
Gray, J. M., Hill, J.J. and Bargmann, C.I. 2005. “A Circuit for Navigation in Caenorhabditis elegans.” Proceedings of the National Academy of Sciences 102(9): 3184–91.
Guindon, S., Dufayard, J-F. and Lefort, V. 2010. “New Algorithms and Methods to Estimate Maximim-Likelihood Phylogenies Assessing the Performance of PhyML 3.0.” Systematic Biology 59(3): 301–21.
Ha, H-I. et al. 2010. “Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans.” Neuron 68(6): 1173–86.
De Haes, W. et al. 2015. “Functional Neuropeptidomics in Invertebrates.” Biochimica et Biophysica Acta - Proteins and Proteomics 1854(7): 812–26. doi:10.1016/j.bbapap.2014.12.011.
Han, L. et al. 2013. “Two Novel DEG/ENaC Channel Subunits Expressed in Glia Are Needed for Nose-Touch Sensitivity in Caenorhabditis elegans.” Journal of Neuroscience 33(3): 936–49.
Harris, G. et al. 2019. “Molecular and Cellular Modulators for Multisensory Integration in C. elegans.” PLoS genetics 15(3): e1007706.
Hilliard, M.A.., Bargmann, C.I. and Bazzicalupo, P.. 2002. “C. elegans Responds to Chemical Repellents by Integrating Sensory Inputs from the Head and the Tail.” Current Biology 12(9): 730–34.
Hobson, R.J. et al. 2006. “SER-7, a Caenorhabditis elegans 5-HT7-like Receptor, Is Essential for the 5-HT Stimulation of Pharyngeal Pumping and Egg Laying.” Genetics 172(1): 159–69.
Hu, Y. et al. 2011. “An Integrative Approach to Ortholog Prediction for Disease-Focused and Other Functional Studies.” BMC Bioinformatics 12.
Husson, S.J. et al. 2005. “Discovering Neuropeptides in Caenorhabditis elegans by Two Dimensional Liquid Chromatography and Mass Spectrometry.” Biochemical and Biophysical Research Communications 335(1): 76–86.
———. 2007. “Neuropeptidergic Signaling in the Nematode Caenorhabditis elegans.” Progress in Neurobiology 82(1): 33–55.
———. 2014. “Worm Peptidomics.” EuPA Open Proteomics 3: 280–90. doi:10.1016/j.euprot.2014.04.005.
Huybrechts, J., De Loof, A. and Schoofs, L. 2004. “Diapausing Colorado Potato Beetles Are Devoid of Short Neuropeptide F I and II.” Biochemical and Biophysical Research Communications 317: 909–16.
Iino, Y., and Yoshida, K. 2009. “Parallel Use of Two Behavioral Mechanisms for Chemotaxis in Caenorhabditis elegans.” Journal of Neuroscience 29(17): 5370–80.
Ikeda, D.D. et al. 2008. “CASY-1, an Ortholog of Calsyntenins/Alcadeins, is Essential for Learning in Caenorhabditis elegans.” PNAS 105(13): 5260–65.
Inagaki, H.K., Panse, K.M., and Anderson, D.J.. 2014. “Independent, Reciprocal Neuromodulatory Control of Sweet and Bitter Taste Sensitivity during Starvation in Drosophila.” Neuron 84(4): 806–20. doi:10.1016/j.neuron.2014.09.032.
Ishihara, T. et al. 2002. “HEN-1, a Secretory Protein with an LDL Receptor Motif, Regulates Sensory Integration and Learning in Caenorhabditis elegans.” Cell 109(5): 639–49.
Jafari, G. et al. 2011. “Regulation of Extrasynaptic 5-HT by Serotonin Reuptake Transporter Function in 5-HT-Absorbing Neurons Underscores Adaptation Behavior in Caenorhabditis elegans.” Journal of Neuroscience 31(24): 8948–57.
Jayakumar, S. et al. 2016. “Drosophila Larval to Pupal Switch under Nutrient Stress Requires IP3R/Ca2+ signalling in Glutamatergic Interneurons.” eLife 5(August): 1–27.
Jehrke, L., Stewart, F.A., Droste, A. and Beller, M.. 2018. “The Impact of Genome Variation and Diet on the Metabolic Phenotype and Microbiome Composition of Drosophila melanogaster.” Scientific Reports 8: 1–15. doi:10.1038/s41598-018-24542-5.
Jekely, G. 2013. “Global View of the Evolution and Diversity of Metazoan Neuropeptide Signaling.” Proceedings of the National Academy of Sciences 110(21): 8702–7. doi:10.1073/pnas.1221833110
Jiang, H.B. et al. 2017. “The Short Neuropeptide F Modulates Olfactory Sensitivity of Bactrocera dorsalis upon Starvation.” Journal of Insect Physiology 99(March): 78–85.
Jin, X., Pokala, N. and Bargmann, C.I. 2016. “Distinct Circuits for the Formation and Retrieval of an Imprinted Olfactory Memory.” Cell 164: 632–43. doi:10.1016/j.cell.2016.01.007.
Johard, H.A.D., Enell, L.E. and Gustafsson, E. 2008. “Intrinsic Neurons of Drosophila Mushroom Bodies Express Short Neuropeptide F : Relations to Extrinsic Neurons Expressing Different Neurotransmitters.” The Journal of Comparative Neurology 507(October): 1479–96.
Johns, S.J. 1996. “TOPO2, Transmembrane Protein Display Software.” http://www.sacs.ucsf.edu/TOPO2/
Jones, S.G., Nixon, K.C.J., Chubak, M.C. and Kramer, J.M. 2018. “Mushroom Body Specific Transcriptome Analysis Reveals Dynamic Regulation of Learning and Memory Genes After Acquisition of Long-Term Courtship Memory in Drosophila.” G3: Genes|Genomes|Genetics 8(November): 3433–46.
Kage, E. et al. 2005. “MBR-1, a Novel Helix-Turn-Helix Transcription Factor, Is Required for Pruning Excessive Neurites in Caenorhabditis elegans.” Current Biology 15(17): 1554–59.
Kahsai, L., Kapan, N. et al. 2010a. “Metabolic Stress Responses in Drosophila Are Modulated by Brain Neurosecretory Cells That Produce Multiple Neuropeptides.” PLoS ONE 5(7).
Kahsai, L., Martin, J.R. and Winther, Å.M.E. 2010b. “Neuropeptides in the Drosophila Central Complex in Modulation of Locomotor Behavior.” Journal of Experimental biology 213: 2256–65.
Käll, L., Krogh, A. and Sonnhammer E.L.L. 2004. “A Combined Transmembrane Topology and Signal Peptide Prediction Method.” Journal of Molecular Biology 338(5): 1027–36.
Kandel, E.R. 2012. “The Molecular Biology of Memory: CAMP, PKA, CRE, CREB-1, CREB-2, and CPEB.” Molecular Brain 5(14)
Kandel, E.R. 2001. “The Molecular Biology of Memory Storage : A Dialogue Between Genes and Synapses.” Science 294(November): 1030–39.
Kaneko, Y., and Hiruma, K. 2014. “Short Neuropeptide F (sNPF) Is a Stage-Specific Suppressor for Juvenile Hormone Biosynthesis by Corpora Allata, and a Critical Factor for the Initiation of Insect Metamorphosis.” Developmental Biology 393(2): 312–19. doi:org/10.1016/j.ydbio.2014.07.014.
Kaniganti, T. et al. 2019. “Sensitivity of Olfactory Sensory Neurons to Food Cues Is Tuned to Nutritional States by Neuropeptide Y Signalling.” bioRxiv. doi:10.1101/573170
Kapustin, Y., Souvorov, A., Tatusova, T. and Lipman, D. 2008. “Splign: Algorithms for Computing Spliced Alignments with Identification of Paralogs.” Biology Direct 3: 1–13.
Katz, M. et al. 2018. “Glia Modulate a Neuronal Circuit for Locomotion Suppression during Sleep in C. elegans.” CellReports 22(10): 2575–83. doi:10.1016/j.celrep.2018.02.036.
Kauffman, A.L. et al. 2010. “Insulin Signaling and Dietary Restriction Differentially Influence the Decline of Learning and Memory with Age.” PLoS biology 8(5).
Klein, M. et al. 2017. “Exploratory Search during Directed Navigation in C. elegans and Drosophila Larva.” eLife 6: 1–14.
Knapek, S. et al. 2013. “Short Neuropeptide F Acts as a Functional Neuromodulator for Olfactory Memory in Kenyon Cells of Drosophila Mushroom Bodies.” Annals of Internal Medicine 158(6): 5340–45.
Ko, K.I. et al. 2015. “Starvation Promotes Concerted Modulation of Appetitive Olfactory Behavior via Parallel Neuromodulatory Circuits.” eLife 4: 1–17.
Kobayashi, K. et al. 2016. “Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.” Cell Reports 14(1): 11–21. doi:10.1016/j.celrep.2015.11.064.
Kõressaar, T. et al. 2018. “Primer3-Masker: Integrating Masking of Template Sequence with Primer Design Software.” Bioinformatics 34(11): 1937–38.
Koressaar, T., and Remm, M. 2007. “Enhancements and Modifications of Primer Design Program Primer3.” Bioinformatics 23(10): 1289–91.
Kubiak, T.M. et al. 2003. “Functional Annotation of the Putative Orphan Caenorhabditis elegans G-Protein-Coupled Receptor C10C6.2 as a FLP-15 Peptide Receptor.” Journal of Biological Chemistry 278(43): 42115–20.
Kuneš, J. et al. 2016. “Prolactin-Releasing Peptide: A New Tool for Obesity Treatment.” Journal of Endocrinology 230(2): R51–58.
Larsch, J. et al. 2015. “A Circuit for Gradient Climbing in C. elegans Chemotaxis.” Cell Reports 12(11): 1748–60. doi:10.1016/j.celrep.2015.08.032.
Lavebratt, C. et al. 2006. “Common Neuropeptide Y2 Receptor Gene Variant Is Protective against Obesity among Swedish Men.” International Journal of Obesity 30(3): 453–59.
Lee, K.S. et al. 2004. “Drosophila Short Neuropeptide F Regulates Food Intake and Body Size.” Journal of Biological Chemistry 279(49): 50781–89.
———. 2008. “Drosophila Short Neuropeptide F Signalling Regulates Growth by ERK-Mediated Insulin Signalling.” Nature Cell Biology 10(4): 468–75.
Lee, K.S. et al. 2017. “Serotonin-Dependent Kinetics of Feeding Bursts Underlie a Graded Response to Food Availability in C. elegans.” Nature Communications 8: 1–11. doi:10.1038/ncomms14221.
Lee, R.Y.N. et al. 1999. “EAT-4, a Homolog of a Mammalian Sodium-Dependent Inorganic Phosphate Cotransporter, Is Necessary for Glutamatergic Neurotransmission in Caenorhabditis elegans.” Journal of Neuroscience 19(1): 159–67.
Li, C., and Kim, K.. 2008. “Neuropeptides.” WormBook: 1–36.
———. 2014. “Family of FLP Peptides in Caenorhabditis elegans and Related Nematodes.” Frontiers in Endocrinology 5(OCT): 1–16.
Li, Q., and Liberles, S.D. 2015. “Aversion and Attraction through Olfaction.” Current Biology 25(3): 120–29. doi:10.1016/j.cub.2014.11.044.
Li, Z. et al. 2012. “Dissecting a Central Flip-Flop Circuit That Integrates Contradictory Sensory Cues in C. elegans Feeding Regulation.” Nature Communications 3: 776–78. doi:10.1038/ncomms1780.
Liesch, J., Bellani, L.L. and Vosshall, L.B. 2013. “Functional and Genetic Characterization of Neuropeptide Y-Like Receptors in Aedes aegypti.” PLoS ONE 7(10).
Loch, D., Breer, H. and Strotmann, J.. 2015. “Endocrine Modulation of Olfactory Responsiveness: Effects of the Orexigenic Hormone Ghrelin.” Chemical Senses 40(7): 469–79.
Lowe, T.M., and Eddy, S.R. 1997. “tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence.” Nucleic Acids Research 25(5): 955–64. doi:10.1093/nar/25.5.955.
Lushchak, O.V., Carlsson, M.A., and Nässel D.R.. 2015. “Food Odors Trigger an Endocrine Response That Affects Food Ingestion and Metabolism.” Cellular and Molecular Life Sciences 72(16): 3143–55.
Macosko, E.Z. et al. 2009. “A Hub-and-Spoke Circuit Drives Pheromone Attraction and Social Behaviour in C. elegans.” Nature 458(7242): 1171–75. doi:10.1038/nature07886.
Madeira, F. et al. 2019. “The EMBL-EBI Search and Sequence Analysis Tools APIs in 2019.” Nucleic acids research. doi:10.1093/nar/gkz268.
Malis, D.D. et al. 1999. “Influence of TASP-V, a Novel Neuropeptide Y (NPY) Y2 Agonist, on Nasal and Bronchial Responses Evoked by Histamine in Anaesthetized Pigs and in Humans.” British Journal of Pharmacology 126(4): 989–96.
Marder, E. 2012. “Neuromodulation of Neuronal Circuits: Back to the Future.” Neuron 76(1): 1–11. doi:10.1016/j.neuron.2012.09.010.
Marvin, J.S. et al. 2013. “An Optimized Fluorescent Probe for Visualizing Glutamate Neurotransmission.” 10(2).
McCloskey, R.J., Fouad, A.D., Churgin, M.A. and Fang-Yen, C.. 2017. “ Food Responsiveness Regulates Episodic Behavioral States in Caenorhabditis elegans .” Journal of Neurophysiology 117(5): 1911–34.
McDiarmid, T.A., Yu, A.J. and Rankin, C.H. 2018. “Beyond the Response—High Throughput Behavioral Analyses to Link Genome to Phenome in Caenorhabditis elegans.” Genes, Brain and Behavior 17(3): 1–14.
McDiarmid, T.A., Ardiel, E.L. and Rankin C.H. 2015. “The Role of Neuropeptides in Learning and Memory in Caenorhabditis elegans.” Current Opinion in Behavioral Sciences 2: 15–20. doi:10.1016/j.cobeha.2014.07.002.
McKay, J.P. et al. 2004. “eat-2 and eat-18 Are Required for Nicotinic Neurotransmission in the Caenorhabditis elegans Pharynx.” Genetics 166(1): 161–69.
Meisel, J.D., and Kim, D.H. 2014. “Behavioral Avoidance of Pathogenic Bacteria by Caenorhabditis elegans.” Trends in Immunology 35(10): 465–70. doi:10.1016/j.it.2014.08.008.
Mi, H., Muruganujan, A., Ebert, D. et al. 2019a. “PANTHER Version 14: More Genomes, a New PANTHER GO-Slim and Improvements in Enrichment Analysis Tools.” Nucleic Acids Research 47(D1): D419–26.
Mi, H., Muruganujan, A., Huang, X. et al. 2019b. “Protocol Update for Large-Scale Genome and Gene Function Analysis with the PANTHER Classification System (v.14.0).” Nature Protocols 14(3): 703–21. doi:10.1038/s41596-019-0128-8.
Mikani, A., Wang, Q-S. and Takeda, M.. 2012. “Peptides Brain-Midgut Short Neuropeptide F Mechanism That Inhibits Digestive Activity of the American Cockroach, Periplaneta americana upon Starvation.” Peptides 34(1): 135–44. doi:10.1016/j.peptides.2011.10.028
Mirabeau, O., and Joly, J-S. 2013. “Molecular Evolution of Peptidergic Signaling Systems in Bilaterians.” Proceedings of the National Academy of Sciences 110(22): E2028–37. doi:10.1073/pnas.1219956110.
Mitchell, A.L. et al. 2019. “InterPro in 2019: Improving Coverage, Classification and Access to Protein Sequence Annotations.” Nucleic Acids Research 47(D1): D351–60.
Mori, I., and Ohshima, Y. 1995. “Neural Regulation of Thermotaxis in Caenorhabditis elegans.” Nature 376(July): 344–48.
Morrison, G.E., Wen, J.Y.M., Runciman, S. and Van Der Kooy D. 1999. “Olfactory Associative Learning in Caenorhabditis elegans Is Impaired in lrn-1 and lrn-2 Mutants.” Behavioral Neuroscience 113(2): 358–67.
Morrison, G.E., and Van Der Kooy, D. 2001. “A Mutation in the AMPA-Type Glutamate Receptor, glr-1, Blocks Olfactory Associative and Nonassociative Learning in Caenorhabditis elegans.” Behavioral Neuroscience 115(3): 640–49.
Nagata, S. et al. 2011. “General and Comparative Endocrinology Effects of Neuropeptides on Feeding Initiation in Larvae of the Silkworm, Bombyx mori.” General and Comparative Endocrinology 172(1): 90–95. doi:10.1016/j.ygcen.2011.03.004.
Nagy, S., Raizen, D.M. and Biron, D.. 2014. “Measurements of Behavioral Quiescence in Caenorhabditis elegans.” Methods 68(3): 500–507.
Nässel, D.R., and Wegener C. 2011. “A Comparative Review of Short and Long Neuropeptide F Signaling in Invertebrates: Any Similarities to Vertebrate Neuropeptide Y Signaling?” Peptides 32(6): 1335–55.
Nässel, D.R. et al. 2008. “A Large Population of Diverse Neurons in the Drosophila Central Nervous System Expresses Short Neuropeptide F, Suggesting Multiple Distributed Peptide Functions.” BMC Neuroscience 35: 1–35.
Nathoo, A.N., Moeller, R.A., Westlund, B.A. and Hart, A.C. 2001. “Identification of Neuropeptide-like Protein Gene Families in Caenorhabditis elegans and Other Species.” Proceedings of the National Academy of Sciences 98(24): 14000–5. doi:10.1073/pnas.241231298
Naveilhan, P., Neveu, I., Arenas, E. and Ernfors, P. 1998. “Complementary and Overlapping Expression of Y1, Y2 and Y5 Receptors in the Developing and Adult Mouse Nervous System.” Neuroscience 87(1): 289–302.
Naveilhan, P., Canals, J.M., Arenas, E. and Ernfors, P. 2001. “Distinct Roles of the Y1 and Y2 Receptors on Neuropeptide Y-Induced Sensitization to Sedation.” Journal of Neurochemistry 78(6): 1201–7.
Nawrocki, E.P. et al. 2015. “Rfam 12.0: Updates to the RNA Families Database.” Nucleic Acids Research 43(D1): D130–37.
Niacaris, T. and Avery, L. 2003. “Serotonin Regulates Repolarization of the C. elegans Pharyngeal Muscle.” Journal of Experimental Biology 206(2): 223–31. doi:doi/10.1242/jeb.00101 (July 9, 2018).
Ohno, H. et al. 2014. “Role of Synaptic Phosphatidylinositol 3-Kinase in a Behavioral Learning Response in C. elegans.” Science 345(6194): 313–17.
Onken, H., Moffett, S.B. and Moffett, D.F. 2004. “The Anterior Stomach of Larval Mosquitoes (Aedes aegypti): Effects of Neuropeptides on Transepithelial Ion Transport and Muscular Motility.” Journal of Experimental biology 207: 3731–39.
Oranth, A. et al. 2018. “Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network.” Neuron 100(6): 1414-1428. doi:10.1016/j.neuron.2018.10.024.
Peymen, K. et al. 2014. “The FMRFamide-like Peptide Family in Nematodes.” Frontiers in Endocrinology 5(JUN).
———. 2019a. “Myoinhibitory Peptide Signaling as a Modulator of Aversive Gustatory Learning in C. elegans.” KU Leuven.
———. 2019b. “Myoinhibitory Peptide Signaling Modulates Aversive Gustatory Learning in Caenorhabditis elegans” ed. Gregory S. Barsh. PLOS Genetics 15(2): e1007945.
Pierce-Shimomura, J.T., Morse, T.M. and Lockery, S.R. 1999. “The Fundamental Role of Pirouettes in Caenorhabditis elegans.” Journal of Neuroscience 19(21): 9557–69.
Piggott, B.J. et al. 2011. “The Neural Circuits and Synaptic Mechanisms Underlying Motor Initiation in C. elegans.” Cell 147(4): 922–33.
Pocock, R., and Hobert, O. 2010. “Hypoxia Activates a Latent Circuit for Processing Gustatory Information in C. elegans.” Nature Neuroscience 13(5): 610–14.
Procko, C., Lu, Y., and Shaham, S.. 2011. “Glia Delimit Shape Changes of Sensory Neuron Receptive Endings in C . elegans.” 1381: 1371–81.
———. 2012. “Sensory Organ Remodeling in Caenorhabditis.” Genetics 190(April): 1405–15.
Pruitt, K.D. et al. 2014. “RefSeq: An Update on Mammalian Reference Sequences.” Nucleic Acids Research 42(D1): 756–63.
Raizen, D.M., Lee, R.Y.N. and Avery, L. 1995. “Interacting Genes Required for Pharyngeal Excitation by Motor Neuron MC in Caenorhabditis elegans.” Genetics 141(4): 1365–82.
Raizen, D.M. et al. 2008. “Lethargus Is a Caenorhabditis elegans Sleep-like State.” Nature 451(7178): 569–72.
Rankin, C.H., Beck, C.D.O. and Chiba C.M. 1990. “Caenorhabditis elegans : A New Model System for the Study of Learning and Memory.” Behavioural Brain Research 37: 89–92.
Rhoades, J.L. et al. 2019. “ASICs Mediate Food Responses in an Enteric Serotonergic Neuron That Controls Foraging Behaviors.” Cell 176(January): 85-97.e14.
Roayaie, K., Crump, J.G., Sagasti, A. and Bargmann, C.I. 1998. “The Gα Protein ODR-3 Mediates Olfactory and Nociceptive Function and Controls Cilium Morphogenesis in C. elegans Olfactory Neurons.” Neuron 20(January): 55–67.
Roberts, W.M. et al. 2016. “A Stochastic Neuronal Model Predicts Random Search Behaviors at Multiple Spatial Scales in C. elegans.” eLife 5: 1–41.
Rogers, C. et al. 2003. “Inhibition of Caenorhabditis elegans Social Feeding by FMRFamide-Related Peptide Activation of NPR-1.” Nature Neuroscience 6(11): 1178–85.
Root, C.M., Ko, K.I., Jafari, A. and Wang, J.W. 2011. “Presynaptic Facilitation by Neuropeptide Signaling Mediates Odor-Driven Food Search.” Cell 145(1): 133–44. doi:10.1016/j.cell.2011.02.008.
Rose, J.K, Kaun, K.R., Chen, S.H. and Rankin, C.H. 2003. “GLR-1, a Non-NMDA Glutamate Receptor Homolog, Is Critical for Long-Term Memory in Caenorhabditis elegans.” Journal of Neuroscience 23(29): 9595–99.
Ryan, D.A. et al. 2014. “Sex, Age, and Hunger Regulate Behavioral Prioritization through Dynamic Modulation of Chemoreceptor Expression.” Current Biology 24(21): 2509–17. doi:10.1016/j.cub.2014.09.032.
Santos-Carvalho, A. et al. 2013. “Neuropeptide Y Receptors Y1 and Y2 Are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture.” Investigative Ophthalmology and Visual Science 54(1): 429–43.
Sapunar, D., Vukojević, K., Kostić, S. and Puljak L. 2011. “Attenuation of Pain-Related Behavior Evoked by Injury through Blockade of Neuropeptide y Y2 Receptor.” Pain 152(5): 1173–81.
Sasakura, H., and Mori I. 2013. “Behavioral Plasticity, Learning, and Memory in C. elegans.” Current Opinion in Neurobiology 23(1): 92–99. doi:10.1016/j.conb.2012.09.005.
Schoofs, L., De Loof, A. and Van Hiel, M.B. 2017. “Neuropeptides as Regulators of Behavior in Insects.” Annual Review of Entomology 62(1): 35–52. doi:10.1146/annurev-ento-031616-035500.
Sengupta, P., Chou, J.H. and Bargmann, C.I. 1996. “odr-10 Encodes a Seven Transmembrane Domain Olfactory Receptor Required for Responses to the Odorant Diacetyl.” Cell 84(6): 899–909.
Shaham, S. 2015. “Glial Development and Function in the Nervous System of Caenorhabditis elegans.” Cold Sprint Harbor Perspectives in Biology 7: 1–14.
Shen, R. et al. 2016. “Neuronal Energy-Sensing Pathway Promotes Energy Balance by Modulating Disease Tolerance.” Proceedings of the National Academy of Sciences 113(23): E3307–14.
Shen, Y., Zhang, J., Calarco, J.A. and Zhang Y. 2014. “EOL-1, the Homolog of the Mammalian Dom3Z, Regulates Olfactory Learning in C. elegans.” Journal of Neuroscience 34(40): 13364–70. doi:10.1523/JNEUROSCI.0230-14.2014.
Siddiq, A. et al. 2007. “Single Nucleotide Polymorphisms in the Neuropeptide Y2 Receptor (NPY2R) Gene and Association with Severe Obesity in French White Subjects.” Diabetologia 50(3): 574–84.
Van Sinay, E. et al. 2017. “Evolutionarily Conserved TRH Neuropeptide Pathway Regulates Growth in Caenorhabditis elegans.” PNAS 114(20): 4065–74.
Singh, C., Rihel, J. and Prober, D.A. 2017. “Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling.” Current Biology 27(24): 3796-3811.e5. doi:10.1016/j.cub.2017.11.018.
Stanić, D. et al. 2006. “Characterization of Neuropeptide Y2 Receptor Protein Expression in the Mouse Brain. I. Distribution in Cell Bodies and Nerve Terminals.” The Journal of Comparative Neurology 499: 357–90.
States, D.J., and Gish, W. 1991. “Combined Use of Sequence Similarity and Codon Bias for Coding Region Identification.” Journal of Computational Biology 1(1): 39–50.
Stein, G.M., and Murphy C.T. 2014. “C. elegans Positive Olfactory Associative Memory Is a Molecularly Conserved Behavioral Paradigm.” Neurobiology of Learning and Memory 115: 86–94. doi:10.1016/j.nlm.2014.07.011.
Stetak, A. et al. 2009. “Neuron-Specific Regulation of Associative Learning and Memory by MAGI-1 in C. elegans.” PLoS ONE 4(6).
Styer, K.L. et al. 2008. “Innate Immunity in Caenorhabditis elegans Is Regulated by Neurons Expressing.” Science 322(October): 460–65.
Tachibana, T., and Sakamoto T. 2014. “Functions of Two Distinct ‘Prolactin-Releasing Peptides’ Evolved from a Common Ancestral Gene.” Frontiers in Endocrinology 5(November): 1–12.
Taghert, P.H., and Nitabach, M.N. 2012. “Peptide Neuromodulation in Invertebrate Model Systems.” Neuron 76(1): 82–97. doi:10.1016/j.neuron.2012.08.035.
Talavera, G., and Castresana, J. 2007. “Improvement of Phylogenies after Removing Divergent and Ambiguously Aligned Blocks from Protein Sequence Alignments.” Systematic Biology 56(4): 564–77.
Thibaud-nissen, F., Souvorov, A., Murphy T. et al. 2013. “Eukaryotic Genome Annotation Pipeline.” In: The NCBI Handbook [Internet]. 2nd edition. Bethesda (MD): National Center for Biotechnology Information (US); 2013-.
Tobin, D.M. et al. 2002. “Combinatorial Expression of TRPV Channel Proteins Defines Their Sensory Functions and Subcellular Localization in C. elegans Neurons.” Neuron 35: 307–18.
Tsao, C-H. et al. 2018. “Drosophila Mushroom Bodies Integrate Hunger and Satiety Signals to Control Innate Food-Seeking Behavior.” eLife 7: 1–35.
Untergasser, A. et al. 2012. “Primer3-New Capabilities and Interfaces.” Nucleic Acids Research 40(15): 1–12.
Vukojevic, V. et al. 2012. “A Role for α-Adducin (ADD-1) in Nematode and Human Memory.” EMBO Journal 31(6): 1453–66.
Wakabayashi, T., Kitagawa, I. and Shingai R. 2004. “Neurons Regulating the Duration of Forward Locomotion in Caenorhabditis elegans.” Neuroscience Research 50(1): 103–11.
Wang, Y. et al. 2008. “A Glial DEG/ENaC Channel Functions with Neuronal Channel DEG-1 to Mediate Specific Sensory Functions in C. elegans.” The EMBO Journal 27(18): 2388–99.
Wang, Y., D’Urso, G. and Bianchi, L. 2011. “Knockout of Glial Channel ACD-1 Exacerbates Sensory Deficits in a C. elegans Mutant by Regulating Calcium Levels of Sensory Neurons.” Journal of Neurophysiology 107(1): 148–58.
Waterhouse, A.M. et al. 2009. “Jalview Version 2-A Multiple Sequence Alignment Editor and Analysis Workbench.” Bioinformatics 25(9): 1189–91.
Wen, J.Y.M. et al. 1997. “Mutations That Prevent Associative Learning in C . elegans.” Behavioral Neuroscience 111(2): 354–68.
White, J.G., Southgate, E., Thomson, J.N. and Brenner, S. 1986. “The Structure of the Nervous System of the Nematode Caenorhabditis elegans.” Philosophical Transactions of the Royal Society B: Biological Sciences 314(1165): 1–340. doi:10.1098/rstb.1986.0056.
Yamashita, M. et al. 2013. “Involvement of Prolactin-Releasing Peptide in the Activation of Oxytocin Neurones in Response to Food Intake.” Journal of Neuroendocrinology 25(5): 455–65.
Yan, G. et al. 2017. “Network Control Principles Predict Neuron Function in the Caenorhabditis elegans Connectome.” Nature 550(7677): 519–23. doi:10.1038/nature24056.
You, Y.J., Kim, J., Raizen, D.M. and Avery, L. 2008. “Insulin, cGMP, and TGF-β Signals Regulate Food Intake and Quiescence in C. elegans: A Model for Satiety.” Cell Metabolism 7(3): 249–57.
Zhang, Y., Lu, H. and Bargmann, C.I. 2005. “Pathogenic Bacteria Induce Aversive Olfactory Learning in Caenorhabditis elegans.” Nature 438(7065): 179–84
