Ghosh DD et al. (2017) Curr Opin Neurobiol "Multisensory integration in C. elegans."

Ghosh DD, Harris G, Nitabach MN, Zhang Y

[Curr Opin Neurobiol, 2017]

Multisensory integration is a neural process by which signals from two or more distinct sensory channels are simultaneously processed to form a more coherent representation of the environment. Multisensory integration, especially when combined with a survey of internal states, provides selective advantages for animals navigating complex environments. Despite appreciation of the importance of multisensory integration in behavior, the underlying molecular and cellular mechanisms remain poorly understood. Recent work looking at how Caenorhabditis elegans makes multisensory decisions has yielded mechanistic insights into how a relatively simple and well-defined nervous system employs circuit motifs of defined features, synaptic signals and extrasynaptic neurotransmission, as well as neuromodulators in processing and integrating multiple sensory inputs to generate flexible and adaptive behavioral outputs.

Ghosh DD et al. (2021) Science "C. elegans discriminates colors to guide foraging."

Lee D, Ghosh DD, Nitabach MN, Jin X, Horvitz HR

[Science, 2021]

Color detection is used by animals of diverse phyla to navigate colorful natural environments and is thought to require evolutionarily conserved opsin photoreceptor genes. We report that <i>Caenorhabditis elegans</i> roundworms can discriminate between colors despite the fact that they lack eyes and opsins. Specifically, we found that white light guides <i>C. elegans</i> foraging decisions away from a blue-pigment toxin secreted by harmful bacteria. These foraging decisions are guided by specific blue-to-amber ratios of light. The color specificity of color-dependent foraging varies notably among wild <i>C. elegans</i> strains, which indicates that color discrimination is ecologically important. We identified two evolutionarily conserved cellular stress response genes required for opsin-independent, color-dependent foraging by <i>C. elegans</i>, and we speculate that cellular stress response pathways can mediate spectral discrimination by photosensitive cells and organisms-even by those lacking opsins.

Ghosh DD et al. (2016) Neuron "Neural Architecture of Hunger-Dependent Multisensory Decision Making in C.elegans."

Chase DL, Sanders T, Hong S, Ghosh DD, Koelle MR, Nitabach MN, McCurdy LY, Cohen N

[Neuron, 2016]

Little is known about how animals integrate multiple sensory inputs in natural environments to balance avoidance of danger with approach to things of value. Furthermore, the mechanistic link between internal physiological state and threat-reward decision making remains poorly understood. Here we confronted C.elegans worms with the decision whether to cross a hyperosmotic barrier presenting the threat of desiccation to reach a source of food odor. We identified a specific interneuron that controls this decision via top-down extrasynaptic aminergic potentiation of the primary osmosensory neurons to increase their sensitivity to the barrier. We also establish that food deprivation increases the worm's willingness to cross the dangerous barrier by suppressing this pathway. These studies reveal a potentially general neural circuit architecture for internal state control of threat-reward decision making.

Shim KH et al. (1991) International C. elegans Meeting "CHARACTERIZATION OF UNC-44 cDNA CLONES"

Shim KH, Otsuka AJ

[International C. elegans Meeting, 1991]

The nematode, C. elegans, is an appropriate organism for the study of neuronal development. Some of 302 neurons can be visualized by use of the FITC fluorescence technique. It is of interest to determine how neuronal outgrowth is regulated during development and what mechanisms are involved at the cellular and molecular levels. The mechanisms and the characteristics of the molecules involved in axonal outgrowth are not well known. Mutations in unc-44 result in abnormal interconnections of the nervous system [Hedgecock et al., Devel. Biol. 111, 158-170, (1985)]. For example, the PDE (postdeirid) neurons in unc-44 show various abnormalities. The mutant axons have complex and variable defects including growth along inappropriate lateral, subventral, or subdorsal positions. The phasmid axons terminate just before they enter the ventral nerve cord at the posterior- end of the preanal region. The unc- 44 gene was cloned by transposon tagging [Franco et al., 7th C. elegans Meeting Abs., p. 76 (1989)]. Three cDNA clones were isolated (DD#PA013, DD#PA049, and DD#PA066) and sequence of DD#PA049 is being determined. The cDNA clones, DD#PA049 and DD#PA066 include the region corresponding to tlle insertion in the rhlO13 allele. The restriction map of DD#PA049 is similar to that of DD#PA066, but DD#PA013 showed a different pattern from DD#PA049 and DD#PA066. The cDNA sequence data demonstrate that DD#PA049 and DD#PA066 encode similar proteins, but the 3' untranslated regions are different. Toward the amino terminus, the DD#PA049 potential protein contains a 5-amino acid insertion relative to DD#A066, perhaps produced by alternative splicing.

James Meir et al. (2002) West Coast Worm Meeting "Characterization of mutants regulating synaptic remodeling of DD motor neurons"

Nikki Alvarez, Yishi Jin, James Meir

[West Coast Worm Meeting, 2002]

Information flow of the neural network depends on maintaining the polarity of individual neurons as well as on precise selection of synaptic partners. Certain neurons, however, re-specify their synaptic targets in response to developmental or environmental cues. The development of DD motor neuron circuitry in C. elegansaccounts for a striking example of neural synaptic remodeling (1). DD neurons are born in embryo, and initially form synapses on ventral muscles in L1 stage. During the L1 to L2 transition, DD neurons remove their ventral synapses and re-establish synaptic connection to dorsal muscles without changing their cell morphology. Therefore, DD motor neurons re-specify their synaptic partners by way of reversing their neural polarity. Using a synaptobrevin::gfp fusion marker driven by a DD specific promoter (a generous gift of Chris Li) (2), we are able to follow DD synaptic remodeling event and to search for mutants disrupting the remodeling process. We isolated two mutants, ju298and ju334, both of which have synapse-like puncta along both dorsal and ventral processes of DD neurons in older larvae and adults. Phenotypic analysis of these two mutants suggests that the establishment of DD neuron polarity may require two independent steps separated by the synaptic remodeling event. In L1 larvae of ju298 homozygote, the DD neurons show partial defect in their synaptic pattern, suggesting that ju298 may be required for the polarity establishment in both pre- and post-DD synaptic remodeling. ju298 maps to the center of chromosome I. In ju334 mutant, although the distribution of the synapse-like puncta in adult DD neurons is similar to that in ju298, the polarity of DD neurons in L1 larvae and the onset of DD remodeling appear to be normal. ju334 may be specifically required for DD neuron polarity establishment in the post- but not pre-DD synaptic remodeling. We mapped ju334between -2.66 and -2.95 on chromosome X, and are currently performing transgenic rescuing experiments.

Julie McCleery et al. (2002) West Coast Worm Meeting "Synaptic remodeling of the DD motor neurons in C. elegans"

Julie McCleery, Yishi Jin

[West Coast Worm Meeting, 2002]

Neuronal dendritic-axonal asymmetry, once established, is normally stabilized in order to maintain information flow. However, changes in neuronal polarity can occur in response to developmental changes or experimental manipulations. The six C. elegans GABAergic DD motor neurons remodel their synaptic connectivity patterns as the worm matures from L1 to L2 stage (1). In L1 worms the DD motor neurons form neuromuscular junctions (NMJs) to ventral muscles. In L2 through adult stages the DD form NMJs along dorsal muscles. We use a synaptobrevin::GFP (SNB-1::GFP) marker to visualize this remodeling event (2, 3). Previous work has shown that DD remodeling does not involve any changes in neuronal morphology, and that lin-14 controls the timing of DD synaptic remodeling (1, 2).

Lee GD et al. (2006) Aging Cell "Dietary deprivation extends lifespan in Caenorhabditis elegans."

Zou S, Wilson MA, Wolkow CA, De Cabo R, Ingram DK, Lee GD, Zhu M

[Aging Cell, 2006]

Dietary restriction (DR) is well known as a nongenetic intervention that robustly extends lifespan in a variety of species; however, its underlying mechanisms remain unclear. We have found in Caenorhabditis elegans that dietary deprivation (DD) during adulthood, defined as removal of their food source Escherichia coli after the completion of larval development, increased lifespan and enhanced thermotolerance and resistance to oxidative stress. DD-induced longevity was independent of one C. elegans SIRTUIN, sir-2.1, which is required for the effects of DR, and was independent of the daf-2/insulin-like signaling pathway that independently regulates longevity and larval diapause in C. elegans. DD did not significantly alter lifespan of fem-1(hc17); eat-2(ad465) worms, a genetic model of DR. These findings suggest that DD and DR share some downstream effectors. In addition, DD was detrimental for longevity when imposed on reproductively active young adults, suggesting that DD may only be beneficial in the absence of competing metabolic demands, such as fertility. Adult-onset DD offers a new paradigm for investigating dietary regulation of longevity in C. elegans. This study presents the first evidence that long-term DD, instead of being detrimental, can extend lifespan of a multicellular adult organism.

Li Z et al. (2016) Neuron "An Elegant Circuit for Balancing Risk and Reward."

Iliff AJ, Xu XZ, Li Z

[Neuron, 2016]

Animals constantly encounter conflicting cues in natural environments. To survive and thrive, they must make appropriate behavioral decisions. In this issue, Ghosh etal. (2016) identified a neural circuit underlying multisensory threat-reward decision making using an elegant C.elegans model.

Valliammai A et al. (2019) Sci Rep "5-Dodecanolide interferes with biofilm formation and reduces the virulence of Methicillin-resistant Staphylococcus aureus (MRSA) through up regulation of agr system."

Krishnan V, Bhaskar JP, Pandian SK, Selvaraj A, Sethupathy S, Priya A, Valliammai A

[Sci Rep, 2019]

Methicillin resistant Staphylococcus aureus (MRSA) is a predominant human pathogen with high morbidity that is listed in the WHO high priority pathogen list. Being a primary cause of persistent human infections, biofilm forming ability of S. aureus plays a pivotal role in the development of antibiotic resistance. Hence, targeting biofilm is an alternative strategy to fight bacterial infections. The present study for the first time demonstrates the non-antibacterial biofilm inhibitory efficacy of 5-Dodecanolide (DD) against ATCC strain and clinical isolates of S. aureus. In addition, DD is able to inhibit adherence of MRSA on human plasma coated Titanium surface. Further, treatment with DD significantly reduced the eDNA synthesis, autoaggregation, staphyloxanthin biosynthesis and ring biofilm formation. Reduction in staphyloxanthin in turn increased the susceptibility of MRSA to healthy human blood and H₂O₂ exposure. Quantitative PCR analysis revealed the induced expression of agrA and agrC upon DD treatment. This resulted down regulation of genes involved in biofilm formation such as fnbA and fnbB and up regulation of RNAIII, hld, psm and genes involved in biofilm matrix degradation such as aur and nuc. Inefficacy of DD on the biofilm formation of agr mutant further validated the agr mediated antibiofilm potential of DD. Notably, DD was efficient in reducing the in vivo colonization of MRSA in Caenorhabditis elegans. Results of gene expression studies and physiological assays unveiled the agr mediated antibiofilm efficacy of DD.

Walthall WW et al. (1995) J Neurosci "Genetic transformation of the synaptic pattern of a motoneuron class in Caenorhabditis elegans."

Plunkett JA, Walthall WW

[J Neurosci, 1995]

Caenorhabditis elegans possesses two classes of inhibitory locomotory neurons, the DD and VD motoneurons (mns), and they form complementary components of a cross-inhibitory neuronal network innervating dorsal and ventral body muscles. The DD and VD mns (collectively called the D mns) share a number of morphological and neurochemical features, and mutations in a number of different genes disrupt both cell types in identical ways; however, the DD and VD mns have different lineal origins and different synaptic patterns. Given the number of phenotypic features shared by the D mns, it was of interest to determine what is responsible for the synaptic patterns that distinguish them. An analysis of the locomotory defect along with a genetic epistasis test suggested that unc-55 mutations alter the function of the VD but not the DD mns. Correlated with the defective locomotory behavior of unc-55 mutants was an alteration in the distribution of varicosities, structures associated with presynaptic elements, on the VD mns. The pattern of varicosities of the unc-55 VD mns resembled that of the wild-type DD mns. Moreover, the selective removal of the DD mns revealed that unc-55 VD mns had adopted a functional role appropriate for the DD mns. Thus, unc-55 appears to be involved in producing the synaptic patterns that distinguish the two D mn classes from one another; when the gene is mutated the VD and DD mns become structurally similar and functionally