An elegant mind: Learning and memory in Caenorhabditis elegans

Abstract

This article reviews the literature on learning and memory in the soil-dwelling nematode Caenorhabditis elegans. Paradigms include nonassociative learning, associative learning, and imprinting, as worms have been shown to habituate to mechanical and chemical stimuli, as well as learn the smells, tastes, temperatures, and oxygen levels that predict aversive chemicals or the presence or absence of food. In each case, the neural circuit underlying the behavior has been at least partially described, and forward and reverse genetics are being used to elucidate the underlying cellular and molecular mechanisms. Several genes have been identified with no known role other than mediating behavior plasticity.Historically, it was believed that even if they were capable of learning, the nervous systems of invertebrates were too different to be instructive on human cognition. In the 1960s, Kandel and colleagues began studying learning in the marine mollusc Aplysia (Kandel and Tauc 1965). Using this system, they were able to relate behavioral plasticity to changes at specific synapses of identified neurons, and began a biochemical analysis of these neuronal changes, uncovering a role for cAMP, PKA, and CREB. In the 1970s, Benzer and colleagues began a genetic dissection of learning in the fruit fly Drosophila melanogaster (Quinn et al. 1974;Dudai et al. 1976). They established an associative learning assay (Quinn et al. 1974) and conducted a forward genetic screen, identifying the first learning mutant, dunce (Dudai et al. 1976). Since then, many genes have been cloned, and the biological basis of learning has proven to be highly conserved (Barco et al. 2006;Skoulakis and Grammenoudi 2006). Today there is no question as to the relevance of invertebrate research in the field of learning and memory.At about the same time that Kandel was beginning his work with Aplysia, Sydney Brenner chose Caenorhabditis elegans as the organism in which to study development and the nervous system (Brenner 1974). Today this transparent nematode is the world's best understood animal. It's small size ( 1 mm), short life cycle (,3 d), and ease of cultivation make it perfect for the laboratory, and its mode of reproduction is ideal for genetic analysis-selffertilizing hermaphrodites can be easily inbred or crossed with males. The genome has been mapped and sequenced, and there are thousands of mutants and RNAi constructs readily available for researchers. Furthermore, C. elegans has an invariant cell lineage and relatively simple morphology-959 cells make up the entire adult hermaphrodite (Sulston and Horvitz 1977;Sulston et al. 1983). Using serial section electron micrographs, White et al. (1986) were able to construct a neural wiring diagram of the hermaphrodite's 302 neurons. They found about 5000 chemical synapses, 600 gap junctions, and 2000 neuromuscular junctions, the location of which were fairly consistent between animals. With its invariant cell lineage and reproducible connectome, C. elegans was initially viewed as a genetically hardwired ...

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“…The animal exhibits several types of quiescence behaviors, which feature characteristics of sleep [31]. Furthermore, the nervous system features habituation as well as simple forms of (associative) learning [2,34]. Single modes of behavior are often controlled by a few neurons that form simple circuits.…”

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“…The simple nervous system of the worm obviously does not lend itself to more complex behaviors. Nonetheless, this has not ruled out the ability of C. elegans researchers to investigate neuronal networks and responses linked to learning paradigms [25][26][27]. Furthermore, pharmacological modulators of neuronal transmission have been applied to identify genes and pathways associated with neurodevelopment and neurotransmitter function and that are conserved with mammalian systems [9].…”