K Oshio et al. (1999) International C. elegans Meeting "Analysis of neuronal connectivity of C. elegans using random walker"

Y Osana, K Kawamura, S Morita, Y Funabashi, K Oshio, K Oka

[International C. elegans Meeting, 1999]

From the detailed report of White et al. and Albertson et al. , we have almost complete knowledge about the synaptic connectivity of C. elegans with the type of synapse (electric junction or chemical synapse). However, the type of each chemical synapse (excitatory or inhibitory one) is not described. Conventional electrophysiological methods for C. elegans is difficult because the size of the neurons is too small to penetrate the intracellular electrode. On the other hand, computational studies of neuronal circuit are now possible by virtue of the above mentioned elaborate experimental studies of neuroanatomists. We have built a new data base of the whole neuronal circuit including pharyngeal neurons only from the article of White et al. and Albertson et al. There exist two other data bases to the knowledge of the present authors. The first data base was constructed by Achacoso and Yamamoto who also analyzed the properties of the network. Another data base was constructed from the article of White et al. by Durbin, which is available on the internet homepage. To begin understanding signal processing on the nervous system, we have investigated the neuronal connectivity by putting random walkers on certain neurons of the network. Here we ignore internal structure of neurons. Random walker is a particle which moves among neurons randomly, and can be considered to be transmitted signal. In our simulation, random walkers are put on certain sensory neurons at each time step, this corresponds to stimulation which sensory neurons accept. We removed random walkers at certain motor neurons, this means, for instance, signals are transmitted to muscles which cause normal action. As a result, we have found that the degree of relation of each neuron for input neurons can be known from the probability to find random walker, although the difference between excitatory and inhibitory of chemical synapses is not taken into account. The simulational results will be shown comparing with real function such as the touch sensitivity. E-mail: oshio@future.st.keio.ac.jp

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.

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)

Chun-Yi Huang et al. (2007) International Worm Meeting "eif-3.K is a pro-apoptotic gene in C. elegans."

Jia-Yun Chen, Yi-Chun Wu, Chun-Yi Huang

[International Worm Meeting, 2007]

Programmed cell death (or apoptosis) is an important feature of C. elegans development. Previous studies have identified pro-apoptotic genes egl-1, ced-3 and ced-4 and anti-apoptotic genes ced-9 and icd-1 that control programmed cell death.. We have identified and characterized a novel pro-apoptotic gene eif-3.K. Loss-of-function by mutation or RNAi inactivation in eif-3.K resulted in a decrease of cell corpses, whereas heatshock-induced over-expression of eif-3.K weakly but significantly increased cell corpses. Interestingly, the eif-3.K mutation partially suppressed ectopic cell deaths caused by over-expression of egl-1 or ced-4. This result suggests that eif-3.K may act downstream of or in parallel to egl-1 and ced-4 in the programmed cell death pathway. Using a cell-specific promoter to express eif-3.k in touch neurons, we showed that eif-3.K likely promoted cell death in a cell-autonomous manner. To further explore EIF-3.K function, we generated antibodies against bacterially expressed EIF-3.K protein. We found that EIF-3.K was ubiquitously expressed during embryogenesis and localized to the cytoplasm. As human eif-3.K can functionally substitute C. elegans eif-3.K in an eif-3.K mutant, the function of eif-3.K in apoptosis is likely conserved in evolution.

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.

Chun-Yi Huang et al. (2006) East Asia C. elegans Meeting "eif-3.K is a pro-apoptotic gene in C. elegans"

Teng-Wei Huang, Chun-Yi Huang

[East Asia C. elegans Meeting, 2006]

Programmed cell death or apoptosis is an important feature during C. elegans development. The pro-apoptotic genes egl-1, ced-4 and ced-3 are required for the execution of cell death. We have identified and characterized a novel pro-apoptotic gene eif-3.K. A loss-of-function mutation or inactivation by RNA interference in eif-3.K resulted in a reduction of cell corpse number during embryogenesis, whereas heatshock-induced over-expression of eif-3.K weakly but significantly promoted programmed cell death. In addition, eif-3.K mutation partially suppressed ectopic cell deaths caused by over-expression of egl-1 and ced-4. This result suggests that eif-3.K may act downstream of or in parallel to egl-1 and ced-4 in the genetic pathway during programmed cell death. Using a cell-specific promoter we showed that eif-3.K likely promoted cell death in a cell-autonomous manner. We generated antibodies against bacterially expressed EIF-3.K protein. The immunostaining result showed that EIF-3.K was ubiquitously expressed during embryogenesis and localized to the cytoplasm. To better understand the cell-death defect of eif-3.K mutants, we are currently performing a 4D microscopic analysis of the cell death process in wild-type and eif-3.K mutants.

Funabashi Y et al. (2000) Japanese Worm Meeting "Similarity and Cluster Analysis of the C.ELEGANS Neural Network"

Funabashi Y, Akiyama E, Kawamura K, Oshio K-i

[Japanese Worm Meeting, 2000]

We classify theoretically the 39 sensory neuron classes of the C. elegans by the analysis of the structure of C. elegans neural network. In the analysis, we first use a random walker model and the connectivity database of the real C. elegans in order to investigate the accessibility from each sensory neuron to other neurons. Next, we classify the sensory neurons by applying cluster analysis to the accessibility data with regard to the sensory neurons. In the above analysis, we consider the data only about the connectivity, not even about the inhibitory / excitatory nature of the synapses; nevertheless, the result of the analysis matches quite well with the experimental results regarding the functions of the sensory neurons. This implies that the topological nature of the structure of the network itself plays an important role in the information processing of the C. elegans neural network.

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).

Funabashi Y et al. (2000) Japanese Worm Meeting "Geometrical Structure of the Neural Network of C. elegans"

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

[Japanese Worm Meeting, 2000]

The soil nematode C. elegans is a small worm with a relatively simple nervous system. The nervous system is separated into two parts. The pharyngeal nervous system is composed of 20 neurons. The connections between these neurons are well documented by Albertson et al. The somatic nervous system consists of 282 neurons, which is nearly completely isolated from the pharyngeal nervous system. The connections of the 282 somatic neurons are studied by White et al. Therefore, all the connections and the architecture of the whole nervous system of the nematode are wellknown. However, the information transmission within the network is yet hardly known. We present a mathematical method to study the global function of the neural network. The real neural network is simplified as graph. A graph is a set of nodes connected to each other by arcs. We here focus on the network of the somatic nervous system. There are 282 nodes and 2268 arcs. We use three indicators to chracterize the graph; (1) vertex degree, (2) distance, and (3) complete subgraphs

Johnson, Christina K. et al. (2019) International Worm Meeting "Requirement of glial Na+/K+-ATPase in touch sensation highlights ionic and metabolic link between glia and touch neurons in C. elegans."

Johnson, Christina K., Bianchi, Laura, Wang, Ying, Fernandez Abascal, Jesus

[International Worm Meeting, 2019]

Isolated microenvironments, such as the tripartite synapse, where the concentration of ions is regulated independently from the surrounding tissues, exist throughout the nervous system, including in mechanoreceptors. Modulation of the ionic composition of these microenvironments has been suggested to be achieved by glia and other accessory cells. However, the molecular mechanisms of ionic regulation and effects on neuronal output and animal behavior are poorly understood. Using the model organism C. elegans, our lab published that Na+ channels of the DEG/ENaC family expressed in glia control neuronal Ca2+ transients and animal behavior in response to sensory stimuli. DEG/ENaC Na+ channels are known to establish a favorable driving force for K+ excretion, which occurs via inward rectifier K+ channels, in epithelial tissues across species. We hypothesized that a similar mechanism exists in the nervous system. Using molecular, genetic, in vivo imaging, and behavioral approaches, we showed that expression in glia of inward rectifier K+ channels and cationic channels rescues the sensory deficits caused by knock-out of glial DEG/ENaCs without disrupting neuronal morphology, supporting our hypothesis. Based on this model, Na+/K+-ATPases are also needed to maintain ionic concentrations following influx of Na+ and excretion of K+. We show here that, in addition to glial Na+ and K+ channels, two specific glial Na+/K+-ATPases, EAT-6 and CATP-1, are needed for touch sensation and that their requirement can be bypassed by a high glucose diet. The effect of glucose is dependent on ATP binding capability of the pump, translation, transcription, and the activity of CATP-2, a third Na+/K+-ATPase ?-subunit. Taken together, our results support metabolic and ionic cooperation between glia and neurons in C. elegans mechanosensors, a mechanism that is essential to regulating neuronal output and may be conserved across species.