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[
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
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[
International C. elegans Meeting,
1999]
A database of synaptic connectivity of 302 neurons of the C. elegans has been constructed[1] from the observations of Albertson and Thomson[2] and White et al.[3] by some of the present authors. A network formed by 302 neurons of the C. elegans is represented on a computer by a network which consists of 302 dots combined by (arrowed) bonds. To analyse the structure of the neural network, behavior of a random walker on it is studied. The walker is displaced among dots which represent neurons over bonds which model synaptic connection. In terms of walking distance defined by minimum time steps which is necessary for the random walker to be displaced between neurons, distances among all neurons, whose synaptic connectivity are described by the above authors, have been determined. Almost all neurons are located within the walking distance of three time steps but walking distance among phalingeal neurons and somatic neurons are more than four time steps. The network is extended in a (more than) nine dimensional space around three nanohedra which are mutually combined by manifolds of less dimension. Each nanohedron consists of nine dots representing interneurons mutually connected by synapses and these nanohedra are located near the center of the network. The lattice is biased by the rectification of the chemical synapse in the sence that a random walker prefers to be displaced from sensory neurons to motor neurons. [1] K. Oshio, S. Morita, Y. Osana and K. Oka: C. elegans connectivity data, Technical report of CCEP, Keio Future No.1 (1998) [2] D. G. Albertson and J. N. Thomson: Phil. Trans R. Soc. Lond. B. 275 (1976) 299 [3] J. G. White, E. Southgate, J. N. Thomson and S. Brenner: Phil. Trans. R. Soc. Lond. B 314 (1986) 1.
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[
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.
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[
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)
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[
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).
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[
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.
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[
International Worm Meeting,
2003]
We present two statistical methods to analyze a partial neural circuit of C. elegans[1].Background: When behavior of C. elegans is studied from the neurobiological viewpoint, we usually focus on a partial neural circuit which is assumed to be closed. That is, only the associated neurons and their connectivity are taken into account. Influence of the remaining neurons of C. elegans is completely neglected. However, there is no guarantee that a result in the closed partial neural circuit is consistent with that in the whole (real) neural circuit since neural information processing is a highly non-linear phenomenon. Although laser ablation experiments of neurons have been performed on C. elegans to identify the associated neurons, this is still a problem in neural modeling.Methods and results: Firstly, all neurons are divided into two complementary groups. One is the neurons which are mainly associated with a certain behavior, and the other is the remaining neurons of C. elegans. Secondly, two popular frameworks in statistical physics are applied to evaluate influence of the remaining neurons on the associated neurons. In our methods, the influence is expressed by a stochastic variable. The structure of the ensemble for the stochastic variable is appropriately evaluated by the neural connectivity of C. elegans. In this way, the degree of freedom in the partial neural circuit, which consists of only the associated neurons, is effectively reduced. We apply the methods to predict the synaptic signs (excitatory or inhibitory) in the touch sensitivity circuit of C. elegans. We find that the influence of the remaining neurons on the touch sensitivity circuit is important to predict the synaptic signs.Database: The synaptic connectivity database[2] is used to determine the connectivity between neurons. This database is created from two memorial papers on the nervous system of C. elegans; Albertson and Thomson (1976), and White et al. (1986). All the chemical synapses and all the gap junctions are exactly listed in this database. Recently, this database is revised. We willingly explain the revised database in addition to the title work.[1] Y. Iwasaki and S. Gomi: submitted to J. theor. Biol; [2] K. Oshio et al.: Technical Report of CCEP, Keio Future, No.1, 1998.
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[
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.
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[
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.
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[
International C. elegans Meeting,
1999]
In this research, we propose an artificial neural network model for touch sensitivity in Caenorhabditis elegans . The neural circuit for touch sensitivity in C.elegans has been examined in detail and is constituted by 66 neurons grouped in 14 classes. The proposed neural network model is directory inspired from the real connectivity data in C. elegans and is based on one of the suitable artificial neural networks, Boltzmann machine. This model has visible units (input units and output units) and invisible units (hidden units). In the nerve system of C. elegans , we considered that the sensory neurons which receive touch stimulus correspond to the input units, the interneurons correspond to hidden units, and the motor neurons correspond to output units. In this research, for simplicity, each unit in the proposed neural network model corresponds to a neuron class instead of a neuron. That is, the neural network model is composed of four input units (ALM, AVM, PLM, PVM), five hidden units (AVA, AVB, AVD, LUA, PVC) and five output units (AS, DA, DB, VA, VB). The values of connection weights which correspond to synapses are determined under the constraint of the connectivity observed in C. elegans by Hebbian-like learning algorithm as same as in the conventional Boltzmann machine . We carried out a series of computer simulations and showed that the proposed model replicates the similar behaviors observed in the real C.elegans . In the simulations, after the values of connection weights in the proposed model are determined, when the sensory neurons for anterior touch ALM and AVM are stimulated, the motor neurons for backward movement AS, DA and VA are excited. In the same way, when the sensory neurons for posterior touch PLM and PVM are stimulated, the motor neurons for forward movement DB and VB are excited. We also compared the lesion test in the proposed model with the laser ablation test in the real C.elegans . As in real C.elegans , the simulation results show that AVD and PVC interneurons are essential for backward and forward movement, respectively.