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[
West Coast Worm Meeting
]
Are there multi-neuron computational modules in the C. elegans nervous system? We attempt to answer this question by applying a systematic statistical approach to the C. elegans wiring diagram (White et al. 1976). Our approach is to identify multi-neuron inter-connectivity patterns that are significantly over-represented in the actual wiring diagram compared to the randomized wiring diagram, which preserves the number of synapses per neuron but not the identity of connections. To do this we compute the numbers of occurrences of all n-neuron (n=2...5) inter-connectivity patterns in the actual and randomized wiring diagrams. This statistical approach confirms previous reports of the over-abundance of reciprocal connections and triangular connectivity patterns (White et al. 1976). Moreover, we discover several new four-neuron and five-neuron inter-connectivity patterns that appear significantly more often in C. elegans than in randomized wiring diagrams. We suggest that these inter-connectivity patterns may serve as computational modules that perform stereotypical functions.
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[
West Coast Worm Meeting,
2002]
Are there multi-neuron computational modules in the C. elegans nervous system? We attempt to answer this question by applying a systematic statistical approach to the C. elegans wiring diagram (White et al. 1976). Our approach is to identify multi-neuron inter-connectivity patterns that are significantly over-represented in the actual wiring diagram compared to the randomized wiring diagram, which preserves the number of synapses per neuron but not the identity of connections. To do this we compute the numbers of occurrences of all n-neuron (n=2...5) inter-connectivity patterns in the actual and randomized wiring diagrams. This statistical approach confirms previous reports of the over-abundance of reciprocal connections and triangular connectivity patterns (White et al. 1976). Moreover, we discover several new four-neuron and five-neuron inter-connectivity patterns that appear significantly more often in C. elegans than in randomized wiring diagrams. We suggest that these inter-connectivity patterns may serve as computational modules that perform stereotypical functions.
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[
International Worm Meeting,
2015]
A connectome is a comprehensive map of all neural connections in an organism's nervous system. The first connectome was published almost 30 years ago by White et al. (1986) and described the structure of the nervous system of the nematode C. elegans adult hermaphrodite. Subsequent network analyses of this data have focused only on the synaptic connectivity of the nervous system, while neglecting much of the spatial information in the data. Initial spatial analyses of the C. elegans connectome reported in (White et al., 1983; Durbin, 1987) used only a sparse sampling of physical neuron contacts. Using the original electron micrographs from (White et al., 1986), we have extended this analysis by performing a 3D reconstruction of every neuron in the C. elegans nerve ring in both the L4 and adult. This represents the first complete volumetric reconstruction of the main neuropil of any animal from multiple developmental stages. With this enriched data set, we have been able to do a comparative analysis of synaptic connectivity, characterize the spatial distribution of synapses for each neuron and analyse the relationship between neuron contact and synapse formation in the C. elegans nerve ring. Similar to (White et al., 1983), we found that ~40% of all possible physical contacts result in a synapse or gap junction. We also found a positive correlation between the frequency of synapse formation and the amount of physical contact between neurons. Specifically, the frequency of synapse formation between two neurons approaches ~0.7 as the amount of physical contact approaches 10% of a neuron's total measured surface area. However, like (Durbin, 1987), we find that synapse probability and synapse number between any pair neurons does not depend strongly on the amount of shared physical contact. Furthermore, synapse volumes appear to be conserved between the L4 and adult, while the number of synapses between any two neurons appear to be, on average, greater in the adult. This could suggest that during late nervous system development, synaptic partnerships are reinforced by creating additional small synapses between neurons rather than enlarging the volume of current synapses. .
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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 Worm Meeting,
2007]
Caenorhabditis elegans embryos undergo stereotypic cell division patterns. Because the cleavage plane for each cell division is defined by the orientation of the mitotic spindle, positioning of spindle poles, or centrosomes, is crucial to regulate cell division patterns. Previous reports revealed that centrosomes are positioned by interactions between microtubules and the particular region of the cell cortex (1-3). However, a detailed mechanistic understanding of centrosome movement is still limited. As a step to better understand the regulation of centrosome movement in early cell divisions, we are developing a quantitative approach to analyze dynamic movement of centrosomes at high spatial and temporal resolution. 4D images of embryos expressing GFP markers visualizing centrosomes and cell membrane are acquired using a spinning-disc confocal microscope, and positions of individual centrosomes are extracted from each image. Using these positional data, direction and speed of each centrosome movement, and rotation angle and distance of each centrosome pair are quantitatively and statistically analyzed in a 3-dimensional space. We will present our progress on the analysis of wild-type and mutant embryos having spindle orientation defects. 1.Hyman and White (1987) J. Cell Biol. 105:2123-2135. 2.Hyman (1989) J. Cell Biol. 109:1185-1193. 3.Keating and White (1998) J. Cell Sci. 111:3027-3033. .
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[
East Coast Worm Meeting,
1998]
Uncoordinated movement in
unc-37 adults is superficially similar to the impairment observed in
unc-4 animals (1). In
unc-4, loss of coordination results from a specific wiring deficit between interneurons and motorneurons in the ventral nerve cord (3,4). We are currently analyzing the detailed synaptic pattern in an adult
unc-37 nerve cord from serial thin sections. Preliminary data were discussed previously (2). We have now identified the major interneurons and 20 motorneurons in the anterior ventral nerve cord, and have determined their synaptic interactions. The morphological phenotype of
unc-37 is not as limited as the specific wiring defect in
unc-4. Many neurons show minor changes in branching or axon caliber, and there is a wider variety of wiring changes. However, in both mutations the AVB interneurons form inappropriate gap junctions onto class A targets, while AVAs fail to make normal junctions onto these targets. This specific change may explain the similarity in their gross behavioral phenotypes. 1. Pflugrad et al. (1997) Development 124:1699-1709. 2. Hall, German and Miller (1997) 11th Annual C. elegans meeting. 3. J.G. White et al. (1986) Phil. Trans. R. Soc. Lond 314:1-340. 4. J.G. White et al. (1992) Nature 355:838-41.
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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 Worm Meeting,
2003]
Neurons form specific connections that result in a fixed circuitry (Sanes and Yamagata, 1999). The precision of these connections arises from a series of events in development: the initial projection of an axon to a target area, followed by a recognition event between specific cells, ultimately forming a synapse. Significant progress has been made in understanding the molecular basis of axon guidance. However, little is known about how the cells recognize their synaptic targets. C. elegans provide an excellent in vivo system in which to study this question. We are studying selective recognition in the nerve ring, which contains axons from >170 neurons that are interconnected by specific and reproducible synapses (White et al, 1986). We are studying the interaction between the amphid neuron ASJ and its synaptic partner PVQ, whose cell bodies are located in the lumbar ganglia. Each ASJ neuron forms about ten synapses onto the axon of the PVQ neuron, ignoring many other neurons that it contacts in the nerve ring (White et al, 1986). The ASJ cell bodies and axons were brightly labeled with RO9F10.6::GFP, with additional light pharynx expression. The PVQ interneurons and their axons were labeled with C25G6.5::dsRED2. Additional amphid neurons expressed this transgene faintly. Using these markers, we can visualize the fasciculation of ASJ and PVQ axons. To identify genes involved in the targeting and fasciculation of ASJ and PVQ, we performed a screen for mutants in which the fasciculation event was disrupted between ASJ and PVQ, and for mutants that exhibited axon guidance defects in either ASJ or PVQ. We will present the results from this screen. We will also present further characterization of sax mutants (sensory axon guidance), which were identified in a screen for altered ASI axons (Crump and Bargmann, 1997 I.W.M.). The mutant
sax-10 has axon guidance defects in AWB, ASH, ASI and PVQ, yet maintains overall normal nerve ring structure (Kirch et al, 2001 I.W.M). We are using additional markers to study its nerve ring in more detail. Sanes, J. R. and Yamagata M. (1999). Formation of lamina-specific synaptic connections. Curr Opin Neurobiol 9(1): 79-87. White, J. G., E. Southgate, et al. (1986). "The structure of the nervous system of Caenorhabditis elegans." Philos Trans R Soc Lond B Biolo Sci 314(1165): 1-340.
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[
International Worm Meeting,
2005]
Synapse formation is an essential step in neural circuit assembly. Emerging evidence suggests that synapses form between certain cells within particular subcompartments from the outset. In an effort to understand this synaptic specificity, we have expressed a RAB-3::GFP construct in one pair of neurons, AVE(R/L). RAB-3 is a membrane-associated vesicular protein that can be used as a presynaptic marker under fluorescent microscopy (Nonet, personal communication). AVE is a command interneuron that along with AVA and AVD are responsible for backward locomotion in C. elegans. The backward command neuron cell bodies are located in the head of the worm, and their axons extend around the nerve ring and then into the ventral cord. Consistent with AVE's role in integrating sensory information into locomotion, almost all of its postsynapses are made in the nerve ring where synaptic inputs (amphid sensory neurons and interneurons) are located and all of its presynapses are made in the ventral cord where postsynaptic targets (motor neurons) are located. The localization of RAB-3 in AVE has confirmed the observations of electron microscopy experiments showing a polarization of the presynaptic specializations only in the ventral cord (White, 1986). This polarized distribution of pre- and post-synaptic specializations suggests that AVE distinguishes its synaptic input and output cells. We have started to explore the molecular mechanisms that are necessary for this target selection by testing potential candidate genes and by performing a genetic screen. White, J.G., Southgate, E., Thomson, J.N. and Brenner, S., 1986. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. Lond. B Biol. Sci. 314, pp. 1-340.
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Guan, A., Meng, J., Zhen, M., Witvliet, D., Mulcahy, B., Lu, Y., Samuel, A., Wen, Q.
[
International Worm Meeting,
2017]
Throughout development, C. elegans maintains serpentine-like dorsal/ventral bending waves for locomotion. In the adult motor circuit, the cholinergic A- and B-type motor neurons innervate and stimulate dorsal and ventral body wall muscles, whereas the D-type GABAergic motor neurons, receiving inputs from A- and B-type motor neurons, innervate and inhibit muscles on the opposing side. Together, they constitute symmetric motor circuit input to the dorsal and ventral body muscle walls that generates balanced muscle activity (1). The cellular components of motor circuit, however, differ drastically in younger animals. All ventral muscle innervating motor neurons are not born until the mid-first larval stage (L1). Partial EM reconstruction in a previous study (2) showed that in L1 stage, the A- and B-type motor neurons only innervate dorsal body wall muscles, and D-type motor neurons innervate only ventral muscles. It remains unclear when the transition to the adult motor circuit synaptic wiring completes. Regardless, it is difficult to explain how such a circuit can produce the symmetric ventral/dorsal bending that constitutes the undulatory motor behavior. We have undertaken anatomical and functional analyses of the L1 motor circuit. I will present studies that lead to the exclusion of multiple potential mechanisms, and the potential involvement of additional, uncharacterized cells in facilitating ventral muscle contraction in the L1 stage animals. References 1. J. G. White, E. Southgate, J. N. Thomson, S. Brenner, Philos Trans R Soc Lond B Biol Sci 314, 1 (Nov 12, 1986). 2. J. G. White, D. G. Albertson, M. A. Anness, Nature 271, 764 (Feb 23, 1978).