Wen, Quan et al. (2011) International Worm Meeting "Bending waves during C. elegans locomotion are driven by proprioceptive coupling."

Whitesides, George, Butler, Victoria, Gershow, Marc, Liu, Xinyu, Schafer, William, Leifer, Andrew, Fang-Yen, Christopher, Chen, Sway, Wen, Quan, Hulme, Elizabeth, Chklovskii, Dmitri, Samuel, Aravinthan, Wyart, Matthieu

[International Worm Meeting, 2011]

Locomotion requires mechanisms for coordinating motor activity throughout an animal's body. Here, using microfluidic devices to bend specific body regions while monitoring the consequences on the rest of the body, we show that proprioceptive coupling drives and organizes forward locomotion in C. elegans. Proprioceptive feedback compels each body region to bend after and in the same direction as the bending in the anterior neighboring region. To understand how proprioception is integrated into the neuromuscular network, we performed calcium imaging of muscle cells to directly visualize the motor activity along the body of a worm trapped in these microfluidic devices. We used optogenetic stimulation of the motor circuit to interrogate the cellular mechanism of proprioceptive feedback. We found that the cholinergic motor neurons both generate and propagate the proprioceptive signal from anterior to posterior body regions. Moreover, body wall muscles in C. elegans can sustain contraction without synaptic input, thereby requiring motor neurons only to trigger changes in bending states but not to maintain bending. Quantifying our experimental observations enabled us to build a simple mathematical model of locomotion, in which we show that proprioceptive coupling not only organizes the bending wave during locomotion, but also explains gait adaptation when the external load on a moving worm is gradually increased.

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan

Goulding M (2012) Neuron "Motor neurons that multitask."

Goulding M

[Neuron, 2012]

Animals use a form of sensory feedback termed proprioception to monitor their body position and modify the motor programs that control movement. In this issue of Neuron, Wen etal. (2012) provide evidence that a subset of motor neurons function as proprioceptors in C.elegans, where B-type motor neurons sense body curvature to control the bending movements that drive forward locomotion.

Chen, Sway P. et al. (2011) International Worm Meeting "How larvae wiggle: functional analysis of the L1 larva locomotory circuit."

Tang, Anji, Chen, Sway P., Wen, Quan, Samuel, Aravinthan D. T.

[International Worm Meeting, 2011]

At all developmental stages, C. elegans navigates its environment by generating and propagating sinusoidal bending waves along its body. The neural circuit controlling the locomotory behavior, however, changes significantly at the late L1 larval stage [1]. Neuroanatomy shows that almost no cholinergic motor neurons innervate the ventral body wall muscles in the L1 larva, raising the question of how the larva is capable of normal locomotion. Here we hypothesize that ventral body wall muscles in the L1 larva contract by default. During the dorsal muscle contracting phase, DB cholinergic motor neurons activate DD GABAergic motor neurons and cause periodic relaxation of the ventral muscles. This hypothesis is supported by two experimental observations. First, we examined the swimming behavior of GABA-deficient mutant unc-25 in the L1 stage and found that the tail consistently curved to one side. Second, we found that wild-type worms expressing GFP in VNC neurons consistently curved to the ventral side after being paralyzed by ivermectin, a drug that silences the motor circuit but has no effect on muscles. Further optogenetic and calcium imaging experiments will be carried out to quantify and relate motor neuron and muscle activity in the free-moving larva. Our approach will build toward a detailed mechanistic model of L1 locomotion. Hopefully, comparison of L1 and adult worm locomotion will shed light on conserved principles of rhythmic motion in general. 1.White, J.G., et al., The structure of the ventral nerve cord of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci, 1976. 275(938): p. 327-48.

Leifer, Andrew et al. (2011) International Worm Meeting "Shining light on behavior: An optogenetic dissection of neural circuits in freely behaving C. elegans."

Wen, Quan, Samuel, Aravinthan, Clark, Christopher, Leifer, Andrew, Fang-Yen, Christopher, Alkema, Mark

[International Worm Meeting, 2011]

Optogenetics provides a promising new platform for conducting behavioral neuroscience investigations in the nematode Caenorhabditis elegans. The ability to precisely manipulate neural activity in individual neurons in a moving worm allows one to pinpoint the contribution of individual neurons to animal behavior. Previously we developed a high-resolution optogenetic illumination system capable of delivering arbitrary light patterns to targeted cells in a freely moving C. elegans (Leifer and Fang-Yen et al, Nature Methods, 2011). The system, called CoLBeRT, uses a high speed camera and custom computer vision software to monitor the motion of an unrestrained worm. As the worm swims or crawls, the system instructs a digital micromirror device to reflect patterns of blue or green laser light onto specific cellular targets expressing Channelrhdopsin-2 or Halorhodopsin. The system has sufficient accuracy and resolution to stimulate individual mechanosensory neurons while a worm swims. Here we have expanded the CoLBeRT system's capabilities to dissect the motor circuit, mechanosensory circuit and investigate the roles of command interneurons. The system is now able to generate illumination patterns with arbitrary amplitude waveforms and we have adapted the system to work with microfluidic devices. We have used the system to differentiate models of wave propagation in the motor circuit, to study habituation in the mechanosensory circuit and to begin an exploration of the command interneurons. Preliminary evidence suggests that stimulation of the command interneuron AVA modulates the worm's backward velocity.

Xu, Tianqi et al. (2017) International Worm Meeting "Gap junction networks within the motor circuit of C. elegans facilitate undulatory wave propagation."

Xu, Tianqi, Zhen, Mei, Wu, Min, Wen, Quan, Po, Michelle, Shao, Shuai, Huo, Jing

[International Worm Meeting, 2017]

Gap junction communication between neurons is prevalent in the motor circuit of invertebrates and vertebrates, yet how electrical couplings might control and coordinate locomotion during normal animal behavior remains largely elusive. The anatomical wiring diagram of C. elegans nervous system suggests that (1) the command interneuron AVB makes en passant electrical synapses with most B-type motor neurons distributed along the worm body; (2) nearby B-type motor neurons are also electrically coupled. What are the functions of gap junction highway and byway in the worm motor circuit? By combining genetic analysis, optogenetic manipulation and computational modeling, we first showed that AVB-B electrical inputs induced a bifurcation in B motor neuron dynamics, and they work synergistically with proprioceptive couplings to enhance sequential activation of motor activities and to equalize the bending amplitude along the worm body. Second, weak electrical couplings between B motor neurons could retrogradely mediate the dynamics of head bending activities. Taken together, gap junction networks within the worm motor circuit facilitate a well-formed and flexible body undulation to propagate from head to tail during C. elegans forward locomotion.

Fang-Yen, Christopher et al. (2009) International Worm Meeting "The worms crawl in, the worms crawl out: An analysis of C. elegans locomotory gaits."

Wen, Quan, Samuel, Aravinthan, Kawai, Risa, Fang-Yen, Christopher, Wyart, Matthieu, Chen, Sway, Chklovskii, Dmitri

[International Worm Meeting, 2009]

C. elegans exhibits very different locomotory patterns when swimming in fluids and crawling on a solid substrate. Compared with crawling, swimming is characterized by a longer wavelength and higher frequency of undulations. We are interested in understanding how a single circuit composed of command neurons, motor neurons, and muscles is capable of supporting these two locomotory gaits. We estimate that when crawling on moist surfaces, worms are held by capillary forces up to 100,000 times greater than the viscous forces experienced during swimming. To investigate in more detail the effect of this mechanical loading on locomotion, we immerse worms in solutions of varying viscosity and measure their wavelength, frequency, and curvature by machine vision algorithms. We show that worm exhibit a continuous transition from swimming to crawling behavior as viscosity is increased from that of water to a value 5 orders of magnitude larger. Worms in fluids of intermediate viscosity exhibit locomotory patterns intermediate between swimming and crawling. Swimming and crawling can therefore be seen as low-load and high-load limits of a continuum of locomotory patterns. We show that our results can be understood in terms of a biomechanical model of C. elegans locomotion in which the swimming to crawling transition is associated with a transition between elastic-dominated and viscous-dominated dynamics. Next we analyze the behavior of worms undergoing spatial transitions between swimming and crawling behaviors, such that mechanical loading varies over the length of the worm. The analysis of such transitions gives insights into the generation and propagation of the sinusoidal bending wave, and the mechanisms of modulation of locomotory gaits. We show that the worm behavior follows neither strictly local nor strictly global modulation, but rather can be described by a set of rules governing the generation and propagation of undulatory waves.

Laskova, Valeriya et al. (2013) International Worm Meeting "Mapping the entire connectome of C. elegans L1 larvae."

Zhen, Mei, Kasthuri, Bobby, Shalek, Richard, Lichtman, Jeff, Samuel, Aravi, Pfister, Hanspeter, Laskova, Valeriya, Kaynig-Fittkau, Verena, Wen, Quan, Berger, Daniel, Guan, Asuka

[International Worm Meeting, 2013]

To investigate the poorly understood mechanisms of development and function of the nervous system, connections between neurons must be deciphered first. The adult nervous system of C. elegans was mapped to near completion by Dr. John White and his colleagues in 1970s. However, neuronal wiring in C. elegans larvae differs from that of an adult, since it undergoes multiple rounds of neuronal birth, apoptosis and rewiring during development. We utilize an Automatic Tape-Collecting Ultramicrotome (ATUM) to section an entire L1 stage animal into thousands cross-sections, followed by the automated imaging with a scanning electron microscope (SEM) to map an entire neuronal wiring diagram with synaptic resolution. The acquired wiring diagram will guide and be validated by calcium imaging to map the functional connection of the juvenile motor circuit.

Chen, Sway et al. (2015) International Worm Meeting "Functional and anatomical analysis of the L1 motor circuit."

Schalek, Richard, Laskova, Valeriya, Chen, Sway, Cook, Steven, Suriyalaksh, Manusnan, Lichtman, Jeff, Guan, Asuka, Mitchell, James, Neubauer, Marianna, Witvliet, Daniel, Wen, Quan, Zhen, Mei, Samuel, Aravinthan, Lu, Yangning, Mulcahy, Ben

[International Worm Meeting, 2015]

At all developmental stages, C. elegans navigates its environment by generating and propagating bending waves along its body. The neuronal circuit controlling locomotory behavior, however, changes significantly at the end of the L1 larval stage. During the L1 stage, B- and A-type cholinergic motor neurons innervate dorsal body wall muscles but not ventral muscles. D-type GABAergic motor neurons innervate ventral muscles but not dorsal muscles. Calcium imaging and optogenetic stimulation suggest that D-type neurons are inhibitory at the L1 stage, causing ventral muscles to relax. At the L2 stage and beyond, both ventral and dorsal muscles are symmetrically innervated by cholinergic and GABAergic motor neurons, and phasic excitation coupled to contralateral inhibition is thought to be responsible for the propagation of undulatory waves. So how does the worm produce undulatory behavior at the L1 stage given the profound ventral/dorsal asymmetry in excitatory cholinergic and inhibitory GABAergic inputs? To answer this question, we have reconstructed the L1 motor circuit using serial section electron microscopy. We are now using targeted cellular ablation, calcium imaging, and optogenetics to pinpoint the mechanism for ventral muscle contraction, and understand how alternating waves of excitation and relaxation drive undulation during the L1 stage. Our goal is a detailed mechanistic model of L1 locomotion. Comparing the circuit basis of L1 with adult worm locomotion should shed light on conserved principles of rhythmic locomotion and development of motor circuits.

Antebi A et al. (1996) East Coast Worm Meeting "daf-12 Coordinates Multiple Developmental Events"

Hedgecock EM, Antebi A

[East Coast Worm Meeting, 1996]

In the nematode, developmental events within or between tissues are precisely coordinated. The DAF-12 nuclear hormone receptor plays multiple roles in synchronizing development. As a heterochronic regulator, it instructs stage specific programs in both gonad and soma. In the dauer pathway, it selects dauer or continuous development in response to growth conditions. Gonadal, somatic and dauer functions are genetically separable, suggesting a complex locus, and alleles can be grouped into six idealized classes. In collaboration with Don Riddle, Pam Larsen and Wen Hui Yeh, we have begun a molecular analysis of alleles to correlate structure with function. So far, we have found a sharp clustering of alleles which selectively disrupt dauer formation within the zinc fingers of the receptor. A unifying hypothesis is that a hormone, acting through DAF-12 and related receptors, coordinates events in gonad and some, as well as dauer development. We suggest a simple model in which the commitments or starts to each developmental stage are synchronized by a hormonal pulse available to all tissues. Moreover, we propose that the starts to each developmental stage lie between the molts, as judged by new cuticle synthesis in the hypodermic and transitions in the migratory behavior of gonadal leader cells. These "parastages" may more accurately reflect the actual functional boundaries of developmental stages.