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 ...
Developmental delay is common in children deprived of normal sensory stimulation - for example, in premature neonates and some institutionalized children. Touch has emerged as an important modality for the facilitation of growth and development; positive effects of supplemental mechanosensory stimulation have been demonstrated in a wide range of organisms, from worm larvae to rat pups to human infants. Animal models are being used to elucidate the cellular and molecular mechanisms underlying these effects. In rats, the amount of maternal licking received as a pup has a profound impact on the behaviour and physiology of the adult; in the microscopic roundworm Caenorhabditis elegans, physical interactions with other worms promote growth and increase adult responsiveness to mechanosensory stimuli. By understanding the underlying mechanisms, as well as the timing and degree of stimulation required to fully reverse the effects of early childhood deprivation, strategies can be developed to best help those in need.
The nervous system is surrounded by an extracellular matrix composed of large glycoproteins, including perlecan, collagens, and laminins. Glial cells in many organisms secrete laminin, a large heterotrimeric protein consisting of an ␣, , and ␥ subunit. Prior studies have found that loss of laminin subunits from vertebrate Schwann cells causes loss of myelination and neuropathies, results attributed to loss of laminin-receptor signaling. We demonstrate that loss of the laminin ␥ subunit (LanB2) in the peripheral glia of Drosophila melanogaster results in the disruption of glial morphology due to disruption of laminin secretion. Specifically, knockdown of LanB2 in peripheral glia results in accumulation of the  subunit (LanB1), leading to distended endoplasmic reticulum (ER), ER stress, and glial swelling. The physiological consequences of disruption of laminin secretion in glia included decreased larval locomotion and ultimately lethality. Loss of the ␥ subunit from wrapping glia resulted in a disruption in the glial ensheathment of axons but surprisingly did not affect animal locomotion. We found that Tango1, a protein thought to exclusively mediate collagen secretion, is also important for laminin secretion in glia via a collagen-independent mechanism. However loss of secretion of the laminin trimer does not disrupt animal locomotion. Rather, it is the loss of one subunit that leads to deleterious consequences through the accumulation of the remaining subunits.
SummarySensitization is a simple form of behavioral plasticity by which an initial stimulus, often signaling danger, leads to increased responsiveness to subsequent stimuli. Cross-modal sensitization is an important feature of arousal in many organisms, yet its molecular and neural mechanisms are incompletely understood. Here we show that in C. elegans, aversive mechanical stimuli lead to both enhanced locomotor activity and sensitization of aversive chemosensory pathways. Both locomotor arousal and cross-modal sensitization depend on the release of FLP-20 neuropeptides from primary mechanosensory neurons and on their receptor FRPR-3. Surprisingly, the critical site of action of FRPR-3 for both sensory and locomotor arousal is RID, a single neuroendocrine cell specialized for the release of neuropeptides that responds to mechanical stimuli in a FLP-20-dependent manner. Thus, FLP-20 peptides function as an afferent arousal signal that conveys mechanosensory information to central neurons that modulate arousal and other behavioral states.Video Abstract
Habituation is a highly conserved phenomenon that remains poorly understood at the molecular level. Invertebrate model systems, like Caenorhabditis elegans, can be a powerful tool for investigating this fundamental process. Here we established a high-throughput learning assay that used real-time computer vision software for behavioral tracking and optogenetics for stimulation of the C. elegans polymodal nociceptor, ASH. Photoactivation of ASH with ChR2 elicited backward locomotion and repetitive stimulation altered aspects of the response in a manner consistent with habituation. Recording photocurrents in ASH, we observed no evidence for light adaptation of ChR2. Furthermore, we ruled out fatigue by demonstrating that sensory input from the touch cells could dishabituate the ASH avoidance circuit. Food and dopamine signaling slowed habituation downstream from ASH excitation via D1-like dopamine receptor, DOP-4. This assay allows for large-scale genetic and drug screens investigating mechanisms of nociception modulation.
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