Ken-ichi Oshio et al. (2002) Japanese Worm Meeting "Revision of synaptic connectivity database"

Eizo Akiyama, Yuishi Iwasaki, Yuko Osana, Ken-ichi Oshio, Sohei Gomi, Satoru Morita, Kotaro Oka, Kazumi Omata

[Japanese Worm Meeting, 2002]

The synaptic connectivity of C. elegans is well known from observations of the somatic system by White et al. and those of the pharyngeal system by Albertson et al. So far, three databases were constructed for computational usage by Achacoso et al. and Durbin, and recently in WormBase. However, they lack some data such as those in tables of White's paper and those in figures of Albertson's book. Our database (K. Oshio, S. Morita, Y. Osana and K. Oka: Technical Report of CCEP, Keio Future No.1, 1998) includes all data described in White's paper and Albertson's book. Unfortunately, some mistakes were found in the database through private communications with John White who is the author of White's paper and with the users of the database. Thus we have been proceeding with the revision to make it perfect one. We are planning to complete the revision in September 2002. The database should be worthwhile not only for neurophysiological studies, but also for post-genomic interests mediating genomes and behavior.

Kiyoshi Kawamura et al. (2002) Japanese Worm Meeting "Pathways from sensory neurons to motor neurons determined by McCulloch-Pitts algorithm."

Ken-ichi Oshio, Kotaro Oka, Satoru Morita, Yuko Osana, Kiyoshi Kawamura

[Japanese Worm Meeting, 2002]

The following two hypotheses are employed :(1) The coupling coefficient in the McCuloch-Pitts equation for C. elegans is proportional to multiplicity of synaptic connection among neurons. (2) Threshold of excitation is the same for every neuron. Under the condition that a given sensor neurons are always excited, excited interneurons and motor neurons have been determined for various threshold values. Assuming that those neurons which are excited for threshold value more than seven are used for native responses concerned with the sensory neuron, pathways from the sensory neuron to various motor neurons have been determined. Pathways along which signals for refrecting response like foreward and backward movement by posterior and anterior part are different from those used for chemotaxis and thermotaxis. To identify pathways for positive and negative chemotaxis, however, connection by elctrical junction is speculated essentially important. We will present circuit from all sensory neurons to motor neurons from this analysis.

Kiyoshi Kawamura et al. (2004) East Asia Worm Meeting "Anatomical Data of Synaptic Connectivity of C. elegans are Almost Perfectly Self-contained."

Satoru Morita, Kiyoshi Kawamura, Sohei Gomi, Yuishi Iwasaki, Yuko Osana, Kazumi Omata, Ken-ichi Oshio, Eizo Akiyama

[East Asia Worm Meeting, 2004]

The anatomical data of synaptic connectivity of C. elegans has been degitized for research with computers. The set of files are entitled 'The database of Synaptic Connectivity of C. elegans for Computaiton' and electronicaly delivered to request. The data files describe all items involved in the paper of Albertson and Thomson (1976) and that of White et al. (1986). The policy we empolyed on creating the data base was that diagrams and tables in the original paper can be reconstructed uniquely up to topology from the degitized data. Since our database is equivalent to the anatomical data, quality of the latter can be investigated on analysing the former by computer. It has been found that the anatomical data is almost perfectly self-contained except a few inconsistent descriptions such that the neuron class PDE sends 61 synapses to the class DVA while the latter receives only 36 synapses from the former. This is an exceptionally extreme case of inconsistency and number of erroneously described synaptic contacts are several hundred among eight thousand contacts. In addition, it has been found that several inconsistent description can be corrected from consideration of topological nature of processes in a three dimensional space, which is also suggested by the database.

Kotaro Oka et al. (2003) International Worm Meeting "Neuronal Circuit and Native Responses of C. elegans"

Kiyoshi Kawamura, Yasuhiro Funabashi, Sohei Gomi, Yuishi Iwasaki, Eizo Akiyama, Kotaro Oka, Ken-ichi Oshio, Satoru Morita, Kazumi Omata, Yuko Osana

[International Worm Meeting, 2003]

The ultimate goal of the present work is to determine pathways of neuronal signal from sensory neurons to motoneurons in occasion of native responses of C. elegans. The fundamental hypothesis is that the pathways consists of highly multiple synaptic connection among interneurons. The McCulloch-Pitts equation is employed to find out sequence of much synaptic connection from each sensory neuron. Although the McCulloch-Pitts equation cannot be used for simulation of propagation of neuronal signal without knowledge about physical parameters within it, it is useful for the present purpose. The point of the algorithm is ; (i) threshold of menbrain potential is replaced by an integer s which is independent of the neuron and (ii) the coupling coefficient between a pair of neurons is replaced with number of synapses between them. When a sensory neuron is always excited, a stationary distribution of excited neurons is realized. Excited neurons in the stationary state are connected to the sensory neuron by pathways which consist of synaptic connection of multiplicity larger than s. A neuron, which is connected with more than one excited neurons, is also excited when the sum of multiplicity of joined synapses are larger than s. A plan of the neuronal circuit is constructed from neurons, which are excited for s more than six, and synapses connecting them. Interneurons are classified into three groups. Three elementary motions of the worm are defined in terms of motoneurons which are simultaneously excited and its behavior in occasion of native responses is combination of such elementary motions. The number of synapses have been counted using the database constructed by our research group. It is translation from the sketch of neurons published by White et al.. into a digital form.

Medley, Jeffrey et al. (2019) International Worm Meeting "Regulation of ZYG-1/Plk4 levels by proteolysis."

Sebou, Brandon, Song, Mi Hye, Schira, Luke, Medley, Jeffrey, DiPanni, Joseph, Shaffou, Blake

[International Worm Meeting, 2019]

As microtubule-organizing centers, centrosomes must duplicate once per cell cycle to ensure cells enter mitosis with two centrosomes and establish bipolarity. Failure to complete centrosome duplication leads to monopolar spindle formation and cytokinesis failure. Conversely, centrosome amplification leads to chromosome missegregation and genomic instability. Thus, the activity of centrosome duplication factors must be tightly regulated to maintain proper centrosome number and maintain bipolarity. A key mechanism to limit centrosome duplication is the regulated proteolysis of centrosomal proteins. We recently showed that an E3 ubiquitin ligase, the Anaphase Promoting Complex/Cyclosome (APC/C), regulates centrosome duplication through its co-activator FZR-1/Cdh1. ZYG-1, an ortholog of human Plk4, is required for centrosome biogenesis. In zyg-1(it25) mutants, centrosome duplication fails leading to monopolar spindle formation and embryonic lethality. Loss of APC/CFZR-1 function restores centrosome duplication and embryonic viability to zyg-1 mutants. APC/CFZR-1 typically recognizes proteins containing KEN-box or Destruction box (D-box) motifs for proteasomal degradation. Consistently, we found APC/CFZR-1 regulates SAS-5 stability via a KEN-box motif; however, our data indicated that APC/CFZR-1 targets additional factors to regulate centrosome duplication. While SAS-5 and the recently identified SAS-7 are the only core centrosome duplication factors containing a KEN-box, other factors contain at least one putative D-box. In this study, we focused on ZYG-1 as a potential substrate of APC/CFZR-1 in centrosome assembly. We observed increased levels of centrosomal ZYG-1 by loss of APC/CFZR-1 supporting our hypothesis that ZYG-1 stability is regulated by APC/CFZR-1-mediated proteolysis. ZYG-1 contains four putative D-boxes that could be targeted by APC/CFZR-1. We used CRISPR/Cas9 genome editing to mutate each D-box motif, and are examining how D-box mutations influence ZYG-1 function. Mutation of one D-box partially restores centrosome duplication and embryonic viability to zyg-1 mutants, presumably through stabilization of ZYG-1. Furthermore, mutating the ZYG-1 D-box together with the SAS-5 KEN-box further restores centrosome duplication and viability to zyg-1 mutants. Thus, our preliminary results are consistent with our hypothesis that, in parallel to KEN-box dependent targeting of SAS-5, APC/CFZR-1 controls ZYG-1 stability through D-box recognition to control proper centrosome number. We are continuing to investigate how APC/CFZR-1 influences ZYG-1 stability through quantitative confocal imaging, genetic and biochemical approaches.

K Omata et al. (1999) International C. elegans Meeting "Habituation of C. elegans for the touch sensitivity"

K Kawamura, F Yonezawa, K Omata

[International C. elegans Meeting, 1999]

In order to study the habituation of C. elegans for the touch sensitivity, we carry out computer simulations, in which the neural circuit is formed by making use of the data table constructed recently by Oshio et al [1]. The i -th neuron is connected with the neighboring j -th neuron through the coupling strength K ij , which is varied dynamically by the Hebb rule. Note that K ij is not necessarily equal to K ji because there are one-way connections between the neurons by chemical synapses. As a reference state, we first deal with the neural circuit consisting only of the neurons ALM, AVM, PLM, PVM, AVA, AVB, PVC, AVD, A and B, that are related to the forward and backward movement directly. We give periodic stimuli to the sensory neurons PLM, PVM, and monitor the response of the motor neuron A. We find that the frequency of the response decreases with time, which indicates that the habituation to the touch sensitivity actually takes place. As one deviation from the reference state, we kill the inter-neuron AVD, and perform the same analysis described in the above. There is a tendency that the decay of the response curve becomes faster, and the habituation is enhanced. As the other deviations, there are several possibilities of killing the inter-neurons AVA, AVB, PVC and/or AVD. We discuss the enhancement of the habituation in relation with the recent experimental results by Hosono. [1.] K. Oshio, S. Morita, Y. Osana and K. Oka; C. elegans synaptic connectivity data'', Technical Report, CCEP, Keio Future No.1 (1998)

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).

Osana Y et al. (2000) Japanese Worm Meeting "Overall Morphology of the C. elegans Neural Circuit"

Oka K, Oshio K-i, Kawamura K, Omata K, Morita S, Osana Y

[Japanese Worm Meeting, 2000]

To study the overall structure of the C. elegans neural circuit, we have carried out cluster analyses on the basis of the neuronal-connectivity database constructed by Oshio et al. . The analyses regard on the connectional multiplicities of the chemical synapses and gap junctions, and the circuit is subjected to thresholds for the multiplicities. With decreasing the thresholds, the number of connections is increased, and the size of the largest neuronal cluster increases gradually until a prominent growth occurs, indicating that the natural circuit without thresholds is a supercritical network'. The critical point provides an index for the determination of an appropriate threshold from which the simplified backbone circuit is derived. We find that there are roughly four indepenent streams in the circuit. Each stream has indivisual functions such as mechanical sensation, chemotaxis, thermotaxis and so forth, and the neurons controlling these functions are specified in the backbone structures. We suggest that the collective properties of the neurons play essential roles for the circuit activity, and the global backbone circuit derived from our analyses explore the possibilities for future experimental studies.

Ali Khan L et al. (1997) International C. elegans Meeting "MATERNAL GENE EMB-8 IS NECESSARY FOR ASYMMETRIC DISTRIBUTION OF DEVELOPMENTAL POTENTIALS IN EARLY C. ELEGANS EMBRYOS"

Siddiqui SS, Ali Khan L, Ali MY, Miwa J, Kikuno R, Kohara Y, Siddiqui ZK

[International C. elegans Meeting, 1997]

A number of observations suggest that emb-8 gene plays critical roles in C. elegans development. At non-permissive temperature, emb-8 embryos divides symmetrically; in 50% the first division produces two equal sized cells, and in the second cleavage both of these cells divide symmetrically again to produce four equal sized cells. In some embryos, these four cells fuse togather and produce two asymmetric cells. emb-8 variably mislocalizes P-granules, they are uniformly distributed in 1-cell embryos, are localized on both anterior AB, and posterior P1 cells of the 2-cell embryos, and are found in all four blastomeres of the 4-cell embryos. Crittenden et al., (1996) also observed mislocalization of the P-granules and Glp-1 in emb-8 embryos. emb-8 also appears to control the orientation of early mitotic spindles, similar to the par-3 muatnts (K. Kemphues and others). However complementation tests show that emb-8 and par-3 are different genes. We thank Sarah Crittenden, Judith Kimble and Ken Kemphues for sharing unpublished results.

Iwasaki, Yuishi (2009) International Worm Meeting "Analysis of noise robustness in neural circuit of C. elegans."

Iwasaki, Yuishi

[International Worm Meeting, 2009]

Is a worm''s behavior, which seems to be random walk, deterministic or not? Noise or fluctuation sometimes plays an important role to organize decision or choice behavior. Neurons in C. elegans are believed to be non-spiking and communicate by graded synaptic transmission. In this meaning, the nervous system of C. elegans is not a "digital" control system but an "analogue" control system which seems to be sensitive to noise. In general, noises (fluctuations) are classified into two types. One is external noises for individuals such as environmental noises. For examples, concentration fluctuation in chemicals for chemotaxis and thermal fluctuation for thermotaxis. The other is internal noises in living organisms. For examples, fluctuation in a neuron''s membrane potential and noise in synaptic transmission. To analyze the noise robustness in neural circuit of C. elegans, simulation is carried out using a stochastic differential equation, so-called Langevin equation. As a neural circuit to simulate the dynamics, I focus on that of chemotaxis in this work. The number of chemical synapses and gap junctions is determined from the two databases of the neural connectivity (Oshio et al., 2003; Chen et al., 2006). I analyze the response of the neural circuit against the noises. If the additive noises are supposed to be uncorrelated each other, the law of large numbers naively says that the influence of the noises decreases as the number of connected neurons (elements) increases. In C. elegans, however, the number of connected neurons for a given neuron is not so large since the total number of neurons in the whole nervous system is 302. Therefore the influence of the noises does not sufficiently vanish. This work was supported by MEXT No. 20115004.