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1 - Learning and Memory in the Nematode Caenorhabditis elegans

from Part I - Evolution of Learning Processes

Published online by Cambridge University Press:  26 May 2022

By
Alex J. Yu  and
Catharine H. Rankin
Edited by
Mark A. Krause ,
Karen L. Hollis  and
Mauricio R. Papini
Mark A. Krause
Affiliation:
Southern Oregon University
Karen L. Hollis
Affiliation:
Mount Holyoke College, Massachusetts
Mauricio R. Papini
Affiliation:
Texas Christian University
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Summary

Caenorhabditis elegans is a microscopic, free-living nematode species that has been studied as a model organism for learning and memory. With a nervous system consisting of 302 neurons, its accessible anatomy accommodates an incredible capacity to support a wide range of behaviors to navigate in its surroundings. In this chapter, we review both the classic and cutting-edge studies on learning and memory in C. elegans. These findings illustrate that learning allows C. elegans to adaptively adjust its behaviors to the environment as a result of experiences and plays a key role in promoting the organism’s fitness. Learning and memory in simple organisms like C. elegans is mediated by complex neural and molecular mechanisms. Mechanisms of learning and memory elucidated from C. elegans studies show convergence onto the learning mechanisms discovered in other species, suggesting that a large portion of the neural principles of learning and memory are rooted in evolution.

Keywords

C. eleganslearning and memorynonassociative learningassociative learninglearning mechanismcellular site of learningsignaling pathwayneuromodulation
Type
Chapter
Information
Evolution of Learning and Memory Mechanisms , pp. 15 - 32
Publisher: Cambridge University Press
Print publication year: 2022

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References

Amano, H., & Maruyama, I. N. (2011). Aversive olfactory learning and associative long-term memory in Caenorhabditis elegans. Learning & Memory, 18, 654–665. https://doi.org/10.1101/lm.2224411Google Scholar
Ardiel, E. L., Giles, A. C., Yu, A. J., Lindsay, T. H., Lockery, S. R., & Rankin, C. H. (2016). Dopamine receptor DOP-4 modulates habituation to repetitive photoactivation of a C. elegans polymodal nociceptor. Learning & Memory, 23, 495–503. https://doi.org/10.1101/lm.041830.116Google Scholar
Ardiel, E. L., McDiarmid, T. A., Timbers, T. A., Lee, K. C. Y., Safaei, J., Pelech, S. L., & Rankin, C. H. (2018). Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans. Proceedings of the Royal Society B: Biological Sciences, 285, 20182084. https://doi.org/10.1098/rspb.2018.2084Google Scholar
Ardiel, E. L., Yu, A. J., Giles, A. C., & Rankin, C. H. (2017). Habituation as an adaptive shift in response strategy mediated by neuropeptides. npj Science of Learning, 2, 9. https://doi.org/10.1038/s41539–017-0011-8Google Scholar
Bargmann, C. I. (2006). Chemosensation in C. elegans. WormBook, ed. The C. elegans research community. https://doi.org/10.1895/wormbook.1.123.1, www.wormbook.org.Google Scholar
Beck, C. D., & Rankin, C. H. (1995). Heat shock disrupts long-term memory consolidation in Caenorhabditis elegans. Learning & Memory, 2(3–4), 161–177. https://doi.org/10.1101/lm.2.3-4.161Google Scholar
Beets, I., Janssen, T., Meelkop, E., Temmerman, L., Suetens, N., Rademakers, S., … Schoofs, L. (2012). Vasopressin/oxytocin-related signaling regulates gustatory associative learning in C. elegans. Science, 338, 543–545. https://doi.org/10.1126/science.1226860Google Scholar
Bernhard, N., & van der Kooy, D. (2000). A behavioral and genetic dissection of two forms of olfactory plasticity in Caenorhabditis elegans: Adaptation and habituation. Learning and Memory, 7, 199–212. https://doi.org/10.1101/lm.7.4.199Google Scholar
Biron, D., Wasserman, S., Thomas, J. H., Samuel, A. D. T., & Sengupta, P. (2008). An olfactory neuron responds stochastically to temperature and modulates Caenorhabditis elegans thermotactic behavior. Proceedings of the National Academy of Sciences, 105, 11002–11007. https://doi.org/10.1073/pnas.0805004105Google Scholar
Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics, 77(1), 71–94. www.ncbi.nlm.nih.gov/pubmed/4366476Google Scholar
Byrne, J. H., & Hawkins, R. D. (2015). Nonassociative learning in invertebrates. Cold Spring Harbor Perspectives in Biology, 7, a021675. https://doi.org/10.1101/cshperspect.a021675Google Scholar
The C. elegans Sequencing Consortium. (1998). Genome sequence of the nematode C. elegans: A platform for investigating biology. Science, 282, 2012–2018. https://doi.org/10.1126/science.282.5396.2012Google Scholar
Chen, Z., Hendricks, M., Cornils, A., Maier, W., Alcedo, J., & Zhang, Y. (2013). Two insulin-like peptides antagonistically regulate aversive olfactory learning in C. elegans. Neuron, 77, 572–585. https://doi.org/10.1016/j.neuron.2012.11.025Google Scholar
Cheung, B. H. H., Cohen, M., Rogers, C., Albayram, O., & De Bono, M. (2005). Experience-dependent modulation of C. elegans behavior by ambient oxygen. Current Biology, 15, 905–917. https://doi.org/10.1016/j.cub.2005.04.017Google Scholar
Chew, Y. L., Tanizawa, Y., Cho, Y., Zhao, B., Yu, A. J., Ardiel, E. L., … Schafer, W. R. (2018). An afferent neuropeptide system transmits mechanosensory signals triggering sensitization and arousal in C. elegans. Neuron, 99, 1233–1246.e6. https://doi.org/10.1016/j.neuron.2018.08.003Google Scholar
Clark, D. A., Biron, D., Sengupta, P., & Samuel, A. D. T. (2006). The AFD sensory neurons encode multiple functions underlying thermotactic behavior in Caenorhabditis elegans. Journal of Neuroscience, 26, 7444–7451. https://doi.org/10.1523/JNEUROSCI.1137-06.2006Google Scholar
Das, S., Sadanandappa, M. K., Dervan, A., Larkin, A., Lee, J. A., Sudhakaran, I. P., … Ramaswamia, M. (2011). Plasticity of local GABAergic interneurons drives olfactory habituation. Proceedings of the National Academy of Sciences, 108(36): E646–E654. https://doi.org/10.1073/pnas.1106411108Google Scholar
Fenk, L. A., & de Bono, M. (2017). Memory of recent oxygen experience switches pheromone valence in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 114, 4195–4200. https://doi.org/10.1073/pnas.1618934114Google Scholar
Gray, J. M., Hill, J. J., & Bargmann, C. I. (2005). A circuit for navigation in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 102, 3184–3191. https://doi.org/10.1073/pnas.0409009101Google Scholar
Groves, P. M., & Thompson, R. F. (1970). Habituation: A dual-process theory. Psychological Review, 77(5), 419–450. www.ncbi.nlm.nih.gov/pubmed/4319167Google Scholar
Hart, A. C., Kass, J., Shapiro, J. E., & Kaplan, J. M. (1999). Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron. Journal of Neuroscience, 19, 1952–1958. https://doi.org/10.1523/jneurosci.19-06-01952.1999Google Scholar
Hedgecock, E. M., & Russell, R. L. (1975). Normal and mutant thermotaxis in the nematode Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 72, 4061–4065. https://doi.org/10.1073/pnas.72.10.4061Google Scholar
Hong, M., Ryu, L., Ow, M. C., Kim, J., Je, A. R., Chinta, S., … Kim, K. (2017). Early pheromone experience modifies a synaptic activity to influence adult pheromone responses of C. elegans. Current Biology, 27, 3168–3177.e3. https://doi.org/10.1016/j.cub.2017.08.068Google Scholar
Hukema, R. K., Rademakers, S., & Jansen, G. (2008). Gustatory plasticity in C. elegans involves integration of negative cues and NaCl taste mediated by serotonin, dopamine, and glutamate. Learning and Memory, 15, 829–836. https://doi.org/10.1101/lm.994408Google Scholar
Jin, X., Pokala, N., & Bargmann, C. I. (2016). Distinct circuits for the formation and retrieval of an imprinted olfactory memory. Cell, 164, 632–643. https://doi.org/10.1016/j.cell.2016.01.007Google Scholar
Kano, T., Brockie, P. J., Sassa, T., Fujimoto, H., Kawahara, Y., Iino, Y., … Maricq, A. V. (2008). Memory in Caenorhabditis elegans is mediated by NMDA-type ionotropic glutamate receptors. Current Biology, 18, 1010–1015. https://doi.org/10.1016/j.cub.2008.05.051Google Scholar
Kauffman, A. L., Ashraf, J. M., Corces-Zimmerman, M. R., Landis, J. N., & Murphy, C. T. (2010). Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age. PLoS Biology, 8, e1000372. https://doi.org/10.1371/journal.pbio.1000372Google Scholar
Kindt, K. S., Quast, K. B., Giles, A. C., De, S., Hendrey, D., Nicastro, I., … Schafer, W. R. (2007). Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans. Neuron, 55, 662–676. https://doi.org/10.1016/j.neuron.2007.07.023Google Scholar
Kodama, E., Kuhara, A., Mohri-Shiomi, A., Kimura, K. D., Okumura, M., Tomioka, M., … Mori, I. (2006). Insulin-like signaling and the neural circuit for integrative behavior in C. elegans. Genes and Development, 20, 2955–2960. https://doi.org/10.1101/gad.1479906Google Scholar
Kuhara, A., & Mori, I. (2006). Molecular physiology of the neural circuit for calcineurin-dependent associative learning in Caenorhabditis elegans. Journal of Neuroscience, 26, 9355–9364. https://doi.org/10.1523/JNEUROSCI.0517-06.2006Google Scholar
Kuhara, A., Okumura, M., Kimata, T., Tanizawa, Y., Takano, R., Kimura, K. D., … Mori, I. (2008). Temperature sensing by an olfactory neuron in a circuit controlling behavior of C. elegans. Science, 320, 803–807. https://doi.org/10.1126/science.1148922Google Scholar
Landry, C. D., Kandel, E. R., & Rajasethupathy, P. (2013). New mechanisms in memory storage: PiRNAs and epigenetics. Trends in Neurosciences, 36, 534–542. https://doi.org/10.1016/j.tins.2013.05.004Google Scholar
Lau, H. L., Timbers, T. A, Mahmoud, R., & Rankin, C. H. (2013). Genetic dissection of memory for associative and non-associative learning in Caenorhabditis elegans. Genes, Brain and Behavior, 12, 210–223. https://doi.org/10.1111/j.1601-183X.2012.00863.xGoogle Scholar
Lee, K., & Mylonakis, E. (2017). An intestine-derived neuropeptide controls avoidance behavior in Caenorhabditis elegans. Cell Reports, 20, 2501–2512. https://doi.org/10.1016/j.celrep.2017.08.053Google Scholar
Li, C., Timbers, T. A., Rose, J. K., Bozorgmehr, T., McEwan, A., & Rankin, C. H. (2013). The FMRFamide-related neuropeptide FLP-20 is required in the mechanosensory neurons during memory for massed training in C. elegans. Learning & Memory, 20, 103–108. https://doi.org/10.1101/lm.028993.112Google Scholar
Lim, J. P., Fehlauer, H., Das, A., Saro, G., Glauser, D. A., Brunet, A., & Goodman, M. B. (2018). Loss of CaMKI function disrupts salt aversive learning in C. elegans. Journal of Neuroscience, 38, 6114–6129. https://doi.org/10.1523/JNEUROSCI.1611-17.2018Google Scholar
Lorenz, K. Z. (1981). The foundations of ethology. Springer Vienna. https://doi.org/10.1007/978-3-7091-3671-3Google Scholar
Mita, K., Yamagishi, M., Fujito, Y., Lukowiak, K., & Ito, E. (2014). An increase in insulin is important for the acquisition conditioned taste aversion in Lymnaea. Neurobiology of Learning and Memory, 116, 132–138. https://doi.org/10.1016/j.nlm.2014.10.006Google Scholar
Mohri, A., Kodama, E., Kimura, K. D., Koike, M., Mizuno, T., & Mori, I. (2005). Genetic control of temperature preference in the nematode Caenorhabditis elegans. Genetics, 169, 1437–1450. https://doi.org/10.1534/genetics.104.036111CrossRefGoogle ScholarPubMed
Moore, R. S., Kaletsky, R., & Murphy, C. T. (2019). Piwi/PRG-1 Argonaute and TGF-β mediate transgenerational learned pathogenic avoidance. Cell, 177, 1827–1841.e12. https://doi.org/10.1016/j.cell.2019.05.024Google Scholar
Mori, I., & Ohshima, Y. (1995). Neural regulation of thermotaxis in Caenorhabditis elegans. Nature, 376(6538), 344–348. https://doi.org/10.1038/376344a0Google Scholar
Morrison, G. E., & 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, 640–649. https://doi.org/10.1037/0735-7044.115.3.640Google Scholar
Morrison, G. E., Wen, J. Y. M., Runciman, S., & van der Kooy, D. (1999). Olfactory associative learning in Caenorhabditis elegans is impaired in lrn-1 and lrn-2 mutants. Behavioral Neuroscience, 113, 358–367. https://doi.org/10.1037//0735-7044.113.2.358Google Scholar
Nishijima, S., & Maruyama, I. N. (2017). Appetitive olfactory learning and long-term associative memory in Caenorhabditis elegans. Frontiers in Behavioral Neuroscience, 11, 80. https://doi.org/10.3389/fnbeh.2017.00080Google Scholar
Nuttley, W. M., Atkinson-Leadbeater, K. P., & van der Kooy, D. (2002). Serotonin mediates food-odor associative learning in the nematode Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 99, 12449–12454. https://doi.org/10.1073/pnas.192101699Google Scholar
Nuttley, W. M., Harbinder, S., & van der Kooy, D. (2001). Regulation of distinct attractive and aversive mechanisms mediating benzaldehyde chemotaxis in Caenorhabditis elegans. Learning and Memory, 8, 170–181. https://doi.org/10.1101/lm.36501Google Scholar
Ohnishi, N., Kuhara, A., Nakamura, F., Okochi, Y., & Mori, I. (2011). Bidirectional regulation of thermotaxis by glutamate transmissions in Caenorhabditis elegans. EMBO Journal, 30, 1376–1388. https://doi.org/10.1038/emboj.2011.13Google Scholar
Peymen, K., Watteyne, J., Borghgraef, C., Van Sinay, E., Beets, I., & Schoofs, L. (2019). Myoinhibitory peptide signaling modulates aversive gustatory learning in Caenorhabditis elegans. PLOS Genetics, 15, e1007945. https://doi.org/10.1371/journal.pgen.1007945Google Scholar
Pierce-Shimomura, J. T., Faumont, S., Gaston, M. R., Pearson, B. J., & Lockery, S. R. (2001). The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature, 410, 694–698. https://doi.org/10.1038/35070575Google Scholar
Pinsker, H., Kupfermann, I., Castellucci, V., & Kandel, E. (1970). Habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science, 167, 1740–1742. https://doi.org/10.1126/science.167.3926.1740Google Scholar
Ramaswami, M. (2014). Network plasticity in adaptive filtering and behavioral habituation. Neuron, 82, 1216–1229. https://doi.org/10.1016/j.neuron.2014.04.035Google Scholar
Rankin, C. H., Abrams, T., Barry, R. J., Bhatnagar, S., Clayton, D. F., Colombo, J., … Thompson, R. F. (2009). Habituation revisited: An updated and revised description of the behavioral characteristics of habituation. Neurobiology of Learning and Memory, 92, 135–138. https://doi.org/10.1016/j.nlm.2008.09.012Google Scholar
Rankin, C. H., Beck, C. D., & Chiba, C. M. (1990). Caenorhabditis elegans: A new model system for the study of learning and memory. Behavioural Brain Research, 37, 89–92. https://doi.org/10.1016/0166-4328(90)90074-OGoogle Scholar
Rankin, C. H., & Broster, B. S. (1992). Factors affecting habituation and recovery from habituation in the nematode Caenorhabditis elegans. Behavioral Neuroscience, 106, 239–249. https://doi.org/10.1037/0735-7044.106.2.239Google Scholar
Rankin, C. H., & Wicks, S. R. (2000). Mutations of the Caenorhabditis elegans brain-specific inorganic phosphate transporter eat-4 affect habituation of the tap-withdrawal response without affecting the response itself. Journal of Neuroscience, 20, 4337–4344.Google Scholar
Remy, J. J., & Hobert, O. (2005). Neuroscience: An interneuronal chemoreceptor required for olfactory imprinting in C. elegans. Science, 309, 787–790. https://doi.org/10.1126/science.1114209Google Scholar
Rose, J. K., Kaun, K. R., Chen, S. H., & 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, 9595–9599. https://doi.org/10.1523/JNEUROSCI.23-29-09595.2003Google Scholar
Rose, J. K., Kaun, K. R., & Rankin, C. H. (2002). A new group-training procedure for habituation demonstrates that presynaptic glutamate release contributes to long-term memory in Caenorhabditis elegans. Learning and Memory, 9, 130–137. https://doi.org/10.1101/lm.46802Google Scholar
Rose, J. K., & Rankin, C. H. (2006). Blocking memory reconsolidation reverses memory-associated changes in glutamate receptor expression. Journal of Neuroscience, 26, 11582–11587. https://doi.org/10.1523/JNEUROSCI.2049-06.2006Google Scholar
Saeki, S., Yamamoto, M., & Iino, Y. (2001). Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans. Journal of Experimental Biology, 204(10), 1757–1764. https://doi.org/10.1242/jeb.204.10.1757Google Scholar
Sakai, N., Iwata, R., Yokoi, S., Butcher, R. A., Clardy, J., Tomioka, M., & Iino, Y. (2013). A sexually conditioned switch of chemosensory behavior in C. elegans. PLoS ONE, 8(7): e68676. https://doi.org/10.1371/journal.pone.0068676Google Scholar
Sammut, M., Cook, S. J., Nguyen, K. C. Q., Felton, T., Hall, D. H., Emmons, S. W., … Barrios, A. (2015). Glia-derived neurons are required for sex-specific learning in C. elegans. Nature, 526(7573), 385–390. https://doi.org/10.1038/nature15700Google Scholar
Schulenburg, H., & Félix, M. A. (2017). The natural biotic environment of Caenorhabditis elegans. Genetics, 206, 55–86. https://doi.org/10.1534/genetics.116.195511Google Scholar
Sulston, J. E., Schierenberg, E., White, J. G., & Thomson, J. N. (1983). The embryonic cell lineage of the nematode Caenorhabditis elegans. Developmental Biology, 100, 64–119. https://doi.org/10.1016/0012-1606(83)90201-4Google Scholar
Timbers, T. A., Giles, A. C., Ardiel, E. L., Kerr, R. A., & Rankin, C. H. (2013). Intensity discrimination deficits cause habituation changes in middle-aged Caenorhabditis elegans. Neurobiology of Aging, 34, 621–631. https://doi.org/10.1016/j.neurobiolaging.2012.03.016Google Scholar
Timbers, T. A., & Rankin, C. H. (2011). Tap withdrawal circuit interneurons require CREB for long-term habituation in Caenorhabditis elegans. Behavioral Neuroscience, 125, 560–566. https://doi.org/10.1037/a0024370Google Scholar
Tomioka, M., Adachi, T., Suzuki, H., Kunitomo, H., Schafer, W. R., & Iino, Y. (2006). The Insulin/PI 3-Kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans. Neuron, 51, 613–625. https://doi.org/10.1016/j.neuron.2006.07.024Google Scholar
Torayama, I., Ishihara, T., & Katsura, I. (2007). Caenorhabditis elegans integrates the signals of butanone and food to enhance chemotaxis to butanone. Journal of Neuroscience, 27, 741–750. https://doi.org/10.1523/JNEUROSCI.4312-06.2007Google Scholar
Wen, J. Y. M., Kumar, N., Morrison, G., Rambaldini, G., Runciman, S., Rousseau, J., & Van Der Kooy, D. (1997). Mutations that prevent associative learning in C. elegans. Behavioral Neuroscience, 111, 354–368. https://doi.org/10.1037/0735-7044.111.2.354Google Scholar
White, J. G., Southgate, E., Thomson, J. N., & Brenner, S. (1986). The structure of the nervous system of the nematode Caenorhabditis elegans. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 314, 1–340.Google Scholar
Wicks, S. R., & Rankin, C. H. (1995). Integration of mechanosensory stimuli in Caenorhabditis elegans. Journal of Neuroscience, 15, 2434–2444.Google Scholar
Wu, T., Duan, F., Yang, W., Liu, H., Caballero, A., Fernandes de Abreu, D. A., … Zhang, Y. (2019). Pheromones modulate learning by regulating the balanced signals of two insulin-like peptides. Neuron, 104, 1095–1109.e5. https://doi.org/10.1016/j.neuron.2019.09.006Google Scholar
Yamazoe-Umemoto, A., Fujita, K., Iino, Y., Iwasaki, Y., & Kimura, K. D. (2015). Modulation of different behavioral components by neuropeptide and dopamine signalings in non-associative odor learning of Caenorhabditis elegans. Neuroscience Research, 99, 22–33. https://doi.org/10.1016/j.neures.2015.05.009Google Scholar
Zhang, X., & Zhang, Y. (2012). DBL-1, a TGF-β, is essential for Caenorhabditis elegans aversive olfactory learning. Proceedings of the National Academy of Sciences USA, 109, 17081–17086. https://doi.org/10.1073/pnas.1205982109Google Scholar
Zhang, Y., Lu, H., & Bargmann, C. I. (2005). Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature, 438, 179–184. https://doi.org/10.1038/nature04216Google Scholar

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