K Omata et al. (1999) International C. elegans Meeting "Characterization of the neural circuit of C. elegans: model analysis of the touch response"

F Yonezawa, K Omata, K Kawamura

[International C. elegans Meeting, 1999]

In order to characterize the neural circuit of C. elagans, we construct a simple model by making use of the data table completed recently by Oshio et al . [1]. We assume that the signal of a neuron is calculated by the product of the signals from the neighboring neurons, and we investigate the touch sensitivity to continuous stimuli described by sinusoidal functions as defined in the rage from 0.0 to 1.0. We calculate the responses of the motor neurons by changing the frequencies of the stimuli. In our calculations, we change only the frequency w PLM for the input signal to the sensory neuron PLM, while the frequency for the other sensory neurons ALM, AVM and PVM is fixed to be a same value w 0 . We show that the output signals from the motor neurons A and B oscillate in time. We measure the minima of the oscillation for each w PLM value. The plot of the minima versus w PLM shows different hehaviors for the case of the neuron A and B. As for the signals from the neuron A, the values of the minima are widely distributed between 0.0 and 1.0 for all w PLM . As for the signals from the neuron B, on the other hand, the features are different for different w PLM values. (a) In the high frequency region of w PLM / w 0 0.4, the oscillation is simple harmonic and there exists only one minimum value (I min = 0.0). (b) As w PLM / w 0 is decreased, another minimum appears at a certain frequency, and the bifurcation takes place discontinuously. This behavior is different from usual continuous bifurcation observed in nonlinear systems. After a few discontinuous branching occur, signals with five periods can be seen in the intermediate frequency region of 0.3 w PLM / w 0 w PLM / w 0 [1] K. Oshio et al. ; C. elegans synaptic connectivity data'', Technical Report, CCEP, Keio Future No.1 (1998).

Katzen, A. et al. (2017) International Worm Meeting "Subjective value guides rational foraging decisions in C. elegans."

Glimcher, P., Lockery, S., Katzen, A., Harbaugh, W.

[International Worm Meeting, 2017]

Value-based decision making - choices driven by subjective assessments of utility - is a central function of the brain and the focus of intensive study in mammals. Until now, evidence that nematodes are capable of value-based decision making has mainly been suggestive. However, economists have developed formal procedures for determining whether a consumer's decisions are based on subjective value as opposed to random or capricious impulses. We recently developed microfluidic devices that enable such tests to be performed on nematodes for the first time. The worm is held at the confluence of contiguous streams of high and low quality bacterial food leaving its head free to move. Bacteria concentrations are adjusted by the experimenter to change the relative "prices" of the two foods in terms of number of bacteria consumed per pharyngeal pump. Food concentrations can also be adjusted in tandem to increase or decrease the worm's overall consumption possibilities, i.e. "budget." Consumption is measured by counting pharyngeal pumps recorded electrically. Worms typically fed in both streams, consuming a mixture of high and low quality food that was unique for each combination of price and budget. We found that worms make globally rational choices in that they obey transitivity. That is, for all sets of food mixtures A, B, and C, if A is preferred to B, and B to C, then A is preferred to C. As transitivity is the necessary and sufficient condition for value maximization, these data provide formal evidence that C. elegans exhibits value-based decision making. Further, we found that the olfactory neuron AWC, known to be activated by the sudden absence of food, is required for intact food choice behavior. Surprisingly, however, we found that AWC is also activated by the switch from high quality food to low quality food, even when the two foods are at the same concentration (price). Thus, subjective value may be represented at the level of individual olfactory neurons. Our behavioral and neuronal data are consistent with a model in which olfactory neurons represent the subjective value of the local environment to direct behavior toward preferable mixtures of particular foods. To our knowledge, this is the first formal demonstration of value-based decision making in a genetically tractable model organism with a simple nervous system, opening the door to the discovery of conserved genes and neural circuits for rational decision making.

Mantilla Galindo, Alejandra et al. (2021) International Worm Meeting "Evaluacion del efecto del extracto etanolico de Witheringia coccoloboides sobre agregados de alpha- sinucleína en la cepa NL5901 de Caenorhabditis elegans"

Mantilla Galindo, Alejandra, Sanchez Mora, Ruth Melida, Gonzalez Devia, Johanna Lizeth, Hidalgo Pulido, Karen Lorena

[International Worm Meeting, 2021]

Neurodegenerative diseases (ND) are a public health problem, cause permanent disability and a high cost in health systems. People affected with Parkinson disease have protein deposits of alpha-synuclein (alpha-syn) in brain cells. The use of biological models such as Caenorhabditis elegans (C. elegans) can answer questions that arise day by day for the development of new therapeutic targets for ND. The transgenic strain NL5901 of C. elegans is characterized to have alpha-syn aggregates labeled with yellow fluorescent protein (YFP), which allows to evaluate compounds effect on the physiological characteristics and / or the reduction of protein aggregates alpha-syn in this model. On the other hand, Witheringia coccoloboides (W. coccoloboides) has been described as a promising plant in the palliative treatment of ND and therefore of interest in ethnopharmacology due to its possible neuroprotective action. Therefore, the main objective of this study was to evaluate the effect of the ethanolic extract of leaves of W. coccoloboides on the physiological characteristics and protein aggregates of alpha-syn in the mutant strain NL5901 of C. elegans. The results of the present work show that the ethanolic extract of leaves of W. coccoloboides has a reducing effect of protein aggregates alpha-syn, improving the physiological characteristics of reproduction and motility, as well as, decreasing the levels of Reactive Oxygen Species (ROS) in strain NL5901 of C. elegans. Therefore, it is possible to suggest that the ethanolic extract of leaves of W. coccoloboides has a protective effect on strain NL5901 of C. elegans, probably attributed to the presence of sterols and / or terpenes, flavonoids and alkaloids, which in turn, it is generate a recovery of muscular activity in the egg lay and locomotion, probably all linked, to synergistic interaction of the phytocompounds present in the ethanolic extract of leaves of W. Coccoloboides. Keywords: Witheringia coccoloboides, alpha-synuclein, Parkinson disease, Caenorhabditis elegans

Dustin L Updike et al. (2005) International Worm Meeting "The TIP60/SWR1 Chromatin Remodeling Complex Functions with the Selector Gene PHA-4 to Endow Cells with Pharyngeal Competence"

Dustin L Updike, Susan E Mango

[International Worm Meeting, 2005]

A critical question in developmental biology is how complex programs of gene expression are orchestrated by a class of regulators known as selector genes. Selector genes code for transcription factors that autonomously govern the fates of groups of cells related to each other by virtue of their cell type, position or affiliation to an organ (1). For example, the FoxA transcription factor PHA-4 dictates the identity of cells within the C. elegans pharynx. Embryos that lack pha-4 fail to generate pharyngeal cells, and these cells acquire an alternative ectodermal fate instead (2,3). PHA-4 functions in combination with additional transcription factors to modulate genes at distinct stages and in different cell types during pharyngeal development (4,5). Here we explore the role of PHA-4 during transcriptional regulation. We identified components of the TIP60/SWR1 complex in a screen for loci that interact genetically with PHA-4. The predicted histone acetyltransferase mys-1 and chromatin remodeling factor ssl-1 each enhanced partial loss of pha-4 activity. In other organisms, the SSL-1 complex exchanges nucleosomes with histone H2A for those containing the variant H2Az (6). Nucleosomes containing H2Az appear less stable than those carrying H2A, which may facilitate the subsequent removal of nucleosomes for activation or repression (7). Consistent with this idea, C. elegans H2Az enhances the pharyngeal phenotype of pha-4 alleles, similar to ssl-1. Furthermore, we observe H2Az associated with PHA-4 target promoters in nascent pharyngeal cells. We propose that the MYS-1/SSL-1 chromatin remodeling complex functions with PHA-4 to endow cells with pharyngeal competence by restructuring the chromatin environment around PHA-4 target genes. Chromatin restructuring may render these promoters susceptible to binding by additional transcription factors that modulate pharyngeal gene expression in conjunction with PHA-4.1) R. S. Mann, S. B. Carroll, Curr. Opin. Genet. Dev. 12, 592 (2002). 2) S. E. Mango, E. J. Lambie, J. Kimble, Development 120, 3019 (1994). 3) M. A. Horner et al., Genes Dev. 12, 1947 (1998). 4) J. Gaudet, S. Muttumu, M. Horner, S. E. Mango, PLoS Biol. 2, e352 (2004). 5) W. Ao, J. Gaudet, W. J. Kent, S. Muttumu, S. E. Mango, Science 305, 1743 (2004). 6) G. Mizuguchi, X. Shen, J. Landry, W. H. Wu, S. Sen, C. Wu, Science 303, 343 (2004). 7) D. W. Abbott, V. S. Ivanova, X Wang, W. M. Bonner, J. Ausio, J. Biol. Chem. 276, 945 (2001).

Takao Inoue et al. (2002) West Coast Worm Meeting "lin-17, lin-18 and patterning of the P7.p lineage"

Rashmi Deshpande, Paul W Sternberg, Russell Hill, Takao Inoue

[West Coast Worm Meeting, 2002]

We are interested in patterning of the 2 (secondary) vulval lineages P5.p and P7.p. In the wild-type, P5.p and P7.p produce stereotyped ABCD and DCBA patterns respectively. In lin-17 and lin-18 mutants, the polarity of the P7.p lineage becomes altered. We examined the P7.p lineage in lin-17 (encoding Frizzled Wnt receptor), lin-18 (encoding RYK receptor tyrosine kinase-related protein; W. Katz and P.W.S.), and double mutant using POP-1 (TCF/LEF) antibody staining and cell fate markers ceh-2::yfp and cdh-3::cfp.

Shawn Lockery (2003) International Worm Meeting "Theoretical analysis of locomotory switching in C. elegans"

Shawn Lockery

[International Worm Meeting, 2003]

Locomotory state in C. elegans is thought to be regulated by a network of command interneurons in two functional pools: the forward command neurons AVB and PVC, and the reverse command neurons AVA and AVD. It has been proposed that the circuit functions as a bistable switch in which only one pool is on at a time. This model is consistent with the observation that presumptive depolarization of both pools (by activated glutamate-receptor knock-in) decreases dwell time in the forward state, whereas presumptive hyperpolarization (by reducing tonic glutamate transmission) increases dwell time in the forward state. However, the bistable switch model does not easily account for the paradoxical observation that dwell time in the forward state is decreased whether one kills forward command neurons (AVB) or reverse command neurons (AVA).Here I propose an alternative model based on four assumptions. (1) Neurons switch stochastically between on and off states with a probability that increases with net synaptic input. (2) Forward command neurons act as a single unit, as do reverse command neurons. (3) Units in the model can adopt four activation states: (i) both off, (ii) forward on, reverse off, (iii) reverse on, forward off, (iv) both off. (4) The four activation states correspond, respectively, to the four main locomotory states: stop, forward, reverse, and omega turn. Unit activity is governed by three synaptic parameters: h, net input from sensory systems; w, the strength of the connections from the unit to its partner; and z, the strength of connections among neurons in the same pool. A key feature of the model is that the rate constants for transitions between its states can be expressed terms of the underlying neuronal parameters h, w, and z. This feature, together with the correspondence between activation states in the model and locomotory states in the animal, allows one to predict synaptic strengths in the command network from the rate constants for locomotory state transitions in the animal.Using a curve fitting routine, I adjusted h, w, and z to fit the rate constants for switching between locomotory states measured in real animals. I tested the model by increasing or decreasing h to mimic, respectively, depolarization and hyperpolarization of command neurons. I found that dwell time in the forward state was modulated as in real worms. In a second test, I decreased the values of h, w, and z in the forward unit by 50% to mimic ablation of the forward neuron AVB and found, as expected, that forward dwell time was decreased. Remarkably, mimicking ablation of the reverse neuron AVA also decreased forward dwell time. The new model therefore provides a successful alternative to the bistable switch hypothesis. NIH MH51383.

Maureen M Barr (2001) International C. elegans Meeting "Lov neurotransmission"

Maureen M Barr

[International C. elegans Meeting, 2001]

The nervous system of the adult C. elegans male possesses 381 neurons to the hermaphrodite's 302. These additional sex-specific neurons are required for male mating behaviors, namely, response to hermaphrodite contact, backing, turning, location of vulva (Lov), spicule insertion, and sperm transfer. We are specifically studying Lov behavior at the cellular, genetic, and molecular levels. The HOA and HOB hook neurons are required for Lov behavior (1) and the putative sensory receptor lov-1 is expressed in HOB (2). How does signaling initiated by the LOV-1 receptor culminate in Lov behavior? We are interested in identifying the neurotransmitters and neuropeptides used by the HOA and HOB mechano- and chemosensory neurons, respectively (3). Anne Hart and Arif Nathoo have identified 21 putative n europeptide like protein ( nlp ) genes in C. elegans and made transcriptional GFP fusions (4) which we have screened for expression in the adult male tail. An nlp-8::gfp transcriptional fusion is expressed uniformly throughout the HOB neuron. Expression is also observed in other non-sex, non-stage specific cells. We have constructed a full length nlp-8::gfp translational fusion and observed expression only in HOB, suggesting nlp-8 may be a Lov neuropeptide. We are exploring the role of nlp-8 in Lov behavior using genetic and molecular approaches. Liu, K. S. and P. W. Sternberg. 1995. Neuron 14:79-89. Barr, M. M. and P. W. Sternberg. 1999. Nature 401: 386-389. Sulston, J. E. et al. 1980. Developmental Biology 78:542-576. Nathoo, A., R. Moeller, and A. Hart. 1999. International Worm Meeting abstract 621.

Kulas, Jana et al. (2009) International Worm Meeting "Cytochrome P450-dependent metabolism of poly-unsaturated fatty acids (PUFA) in the nematode Caenorhabditis elegans."

Schmidt, Cosima, Kulas, Jana, Steinberg, Christian, Kosel, Mandy, Rothe, Michael, Menzel, Ralph

[International Worm Meeting, 2009]

We tested here the hypothesis that some of Caenorhabditis elegans cytochrome P450 (CYP) forms may be involved in the metabolism of polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), the predominant PUFA of this nematode. Microsomes isolated from adult worms contained spectrally active CYP proteins and showed NADPH-CYP reductase (CPR) activities. They metabolized EPA and, with lower activity, also arachidonic acid (AA) to specific sets of regioisomeric epoxy- and w-/(w-1)-hydroxy-derivatives. 17(R),18(S)-epoxyeicosatetraenoic acid was produced as the main EPA metabolite with an enantiomeric purity of 72 %. The epoxygenase and hydroxylase reactions were NADPH-dependent, required the functional expression of the CPR-encoding emb-8 gene, and were inhibited by 17-ODYA and PPOH, two compounds known to inactivate mammalian AA-metabolizing CYP isoforms. Multiple followed by single RNAi gene silencing experiments identified CYP-29A3 and CYP-33E2 as the major isoforms contributing to EPA metabolism in C. elegans. Liquid chromatography/ mass spectrometry revealed that regioisomeric epoxy- and hydroxy-derivatives of EPA and AA are endogenous constituents of C. elegans. The endogenous EPA metabolite levels were increased by treating the worms with fenofibrate, which also induced the microsomal epoxygenase and hydroxylase activities. Heterologous expression of cyp-29A3 and cyp-33E2 in SF9 insect cells is in progress. These results demonstrate for the first time that C. elegans shares with mammals the capacity to produce CYP-dependent eicosanoids and may thus facilitate future studies on the mechanisms of action of this important class of signaling molecules.

Barrios A et al. (2010) Biology of the C. elegans Male, Madison, WI "A Sexy Coat"

Barr M M, Barrios A

[Biology of the C. elegans Male, Madison, WI, 2010]

To transmit his genome, the C. elegans male needs to mate with a hermaphrodite. To achieve reproductive success, the male has evolved a wide repertoire of sexual behaviors that rely heavily on sensory stimuli from the hermaphrodite. A blend of secreted short chain ascarosides promotes male aggregation at locations where hermaphrodites are present (Srinivasan, Kaplan et al., 2008). Although this pheromone assists in mate location, hermaphrodite secretions alone are neither sufficient nor necessary to retain males and to suppress male exploratory and mate seeking behavior. For this, contact with an adult hermaphrodite is required (Barrios et al., 2008). Here we present evidence that a pheromone different from that identified by Srinivasan, Kaplan et al. is present on the hermaphrodite cuticle and regulates contact-dependent male sexual behaviors. Using a combination of genetic and chemical manipulations we have perturbed the hermaphrodite cuticle and analyzed their effect on two contact-dependent male sexual behaviors: retention and response. We find that the hermaphrodite cuticle appears to be composed of sexualized chemicals. Males with a feminized hypodermis (by expression of dpy-7::tra-2 IC-construct provided by W. Mowrey and D. Portman) can retain other males andelicit a high level of response to contact, whereas wild type males cannot. Male response efficiency is significantly reduced against surface coat mutant hermaphrodites srf-2, 3 and 5and against hermaphrodites resistant to bacterial adhesion to their cuticle bus-2, 4, 8, 12and 17. These genes encode galactosyl-transferases and sugar transporters, suggesting that the hermaphrodite contact pheromone is a glyco-conjugate. In contrast, daf-22 hermaphrodites, which are defective in the production of the ascaroside blend for aggregation, fully retain males and elicit a wild type male response. In order to chemically isolate the contact-based pheromone we have developed an assay to carry out activity-guided fractionation. We have been able to remove activity from wild type hermaphrodites with organic solvents. Applying this hermaphrodite extract to a bus mutant restores male response to wild type levels. Barrios,A., Nurrish, S. and Emmons, S. W.(2008). Sensory regulation of C. elegans male mate-searching behavior. CurrBiol 18, 1865-71. Srinivasan,J., Kaplan, F., Ajredini, R., Zachariah, C., Alborn, H. T., Teal, P. E., Malik,R. U., Edison, A. S., Sternberg, P. W. and Schroeder, F. C. (2008). A blend of small molecules regulates bothmating and development in Caenorhabditis elegans. Nature454, 1115-8.

Kristy Lawton et al. (2008) C.elegans Neuronal Development Meeting "A Stochastic Model of Command Neuron Function"

Kristy Lawton, Steven Augustine, Shawn Lockery, William Roberts

[C.elegans Neuronal Development Meeting, 2008]

Locomotory state in C. elegans is regulated by a network of forward and reverse command neurons in two reciprocally connected pools, but how this network functions is poorly understood. We propose a model in which the network acts as a stochastic system. The model arises from three simple assumptions: (1) Forward neurons act as a single unit F and reverse neurons act as a single unit R. (2) Unit activation switches stochastically between two activation states: 0 and 1, corresponding to off and on, respectively. (3) The probability of a 0-1 transition is a sigmoidal function of synaptic input, i.e. the weighted sum of presynaptic activation states. Accordingly, there are four possible states of the network: (F,R) = {(0,0), (0,1), (1,0) and (1,1)}. Previous neuronal ablations suggest that the first three correspond, respectively, to locomotory pauses, forward locomotion, and reverse locomotion; we propose that the state (1,1) also corresponds to pauses, as joint activation of forward and reverse motor systems is likely to cancel out. The kinetics of the network are fully described by eight coefficients -- the rate constants K for transitions between pairs of states that differ in the activation level of one (but not both) units. Synaptic interactions in the model are fully described by just six coefficients -- the synaptic weights W, including the four possible connections among and between F and R neurons (Wfr, Wrf, Wff, Wrr), and the two connections from outside the command network (Wxf, Wxr), including sensory inputs. By Assumption 3, simple algebraic relationships can be derived such that given K, W can be computed. Thus, it is theoretically possible to infer command network connectivity from the locomotion behavior. To test such inferences, we reasoned that in strains with chronic depolarization of command neurons, such as nmr-1::GLR-1(A/T), Wxf and Wxr should be more positive than in wild-type worms whereas, in chronically hyperpolarized strains such as eat-4, they should be less positive. Accordingly, using a maximum likelihood approach, we obtained K for spontaneous locomotion in wild-type worms and several depolarized and hyperpolarized strains and computed W''s for each strain. As expected, Wxf and Wxr were shifted positively in depolarizing strains and negatively in hyperpolarizing strains. We conclude that the stochastic switch model provides an intuitive yet predictive representation of command neuron function. NIH MH51383.