Potential role of a ventral nerve cord central pattern generator in forward and backward locomotion in Caenorhabditis elegans

C. elegans locomotes in an undulatory fashion, generating thrust by propagating dorsoventral bends along its body. Although central pattern generators (CPGs) are typically involved in animal locomotion, their presence in C. elegans has been questioned, mainly because there has been no evident circuit that supports intrinsic network oscillations. With a fully reconstructed connectome, the question of whether it is possible to have a CPG in the ventral nerve cord (VNC) of C. elegans can be answered through computational models. We modeled a repeating neural unit based on segmentation analysis of the connectome. We then used an evolutionary algorithm to determine the unknown physiological parameters of each neuron so as to match the features of the neural traces of the worm during forward and backward locomotion. We performed 1,000 evolutionary runs and consistently found configurations of the neural circuit that produced oscillations matching the main characteristic observed in experimental recordings. In addition to providing an existence proof for the possibility of a CPG in the VNC, we suggest a series of testable hypotheses about its operation. More generally, we show the feasibility and fruitfulness of a methodology to study behavior based on a connectome, in the absence of complete neurophysiological details.Author SummaryDespite the relative simplicity of C. elegans, its locomotion machinery is not yet well understood. We focus on the generation of dorsoventral body bends. Although network central pattern generators are commonly involved in animal locomotion, their presence in C. elegans has been questioned due to a lack of an evident neural circuit to support it. We developed a computational model grounded in the available neuroanatomy and neurophysiology, and we used an evolutionary algorithm to explore the space of possible configurations of the circuit that matched the neural traces observed during forward and backward locomotion in the worm. Our results demonstrate that it is possible for the rhythmic contraction to be produced by a circuit present in the ventral nerve cord.

[1]  J. Gray,et al.  THE LOCOMOTION OF NEMATODES. , 1964, The Journal of experimental biology.

[2]  R. Hall,et al.  Relationship of Muscle Apolipoprotein E Expression with Markers of Cellular Stress, Metabolism, and Blood Biomarkers in Cognitively Healthy and Impaired Older Adults , 2023, Journal of Alzheimer's disease : JAD.

[3]  S. Brenner,et al.  The structure of the ventral nerve cord of Caenorhabditis elegans. , 1976, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[4]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[5]  S. Brenner,et al.  The neural circuit for touch sensitivity in Caenorhabditis elegans , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[7]  P. Erdös,et al.  Theory of the locomotion of nematodes: Dynamics of undulatory progression on a surface. , 1991, Biophysical journal.

[8]  P. Erdös,et al.  Theory of the locomotion of nematodes: control of the somatic motor neurons by interneurons. , 1993, Mathematical biosciences.

[9]  Randall D. Beer,et al.  On the Dynamics of Small Continuous-Time Recurrent Neural Networks , 1995, Adapt. Behav..

[10]  S. R. Wicks,et al.  A Dynamic Network Simulation of the Nematode Tap Withdrawal Circuit: Predictions Concerning Synaptic Function Using Behavioral Criteria , 1996, The Journal of Neuroscience.

[11]  Randall D. Beer,et al.  The brain has a body: adaptive behavior emerges from interactions of nervous system, body and environment , 1997, Trends in Neurosciences.

[12]  M. Dimitrijevic,et al.  Evidence for a Spinal Central Pattern Generator in Humans a , 1998, Annals of the New York Academy of Sciences.

[13]  A. V. Maricq,et al.  Neuronal Control of Locomotion in C. elegans Is Modified by a Dominant Mutation in the GLR-1 Ionotropic Glutamate Receptor , 1999, Neuron.

[14]  R. Shingai,et al.  Neural network model to generate head swing in locomotion of Caenorhabditis elegans , 2004, Network.

[15]  E. Marder,et al.  Invertebrate Central Pattern Generation Moves along , 2005, Current Biology.

[16]  D. Chklovskii,et al.  Wiring optimization can relate neuronal structure and function. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Paul W. Sternberg,et al.  Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics , 2007, Journal of Computational Neuroscience.

[18]  John Bryden,et al.  An Integrated Neuro-mechanical Model of C. elegansForward Locomotion , 2007, ICONIP.

[19]  Auke Jan Ijspeert,et al.  Central pattern generators for locomotion control in animals and robots: A review , 2008, Neural Networks.

[20]  A. V. Maricq,et al.  Action potentials contribute to neuronal signaling in C. elegans , 2008, Nature Neuroscience.

[21]  John Bryden,et al.  Neural control of Caenorhabditis elegans forward locomotion: the role of sensory feedback , 2008, Biological Cybernetics.

[22]  S. Lockery,et al.  The quest for action potentials in C. elegans neurons hits a plateau , 2009, Nature Neuroscience.

[23]  N. Cohen,et al.  Forward locomotion of the nematode C. elegans is achieved through modulation of a single gait , 2009, HFSP journal.

[24]  Aravinthan D. T. Samuel,et al.  Biomechanical analysis of gait adaptation in the nematode Caenorhabditis elegans , 2010, Proceedings of the National Academy of Sciences.

[25]  A. Selverston,et al.  Invertebrate central pattern generator circuits , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[26]  S. Lockery,et al.  Evolution and Analysis of Minimal Neural Circuits for Klinotaxis in Caenorhabditis elegans , 2010, The Journal of Neuroscience.

[27]  Michael J. O'Donovan,et al.  Motoneurons Dedicated to Either Forward or Backward Locomotion in the Nematode Caenorhabditis elegans , 2010, The Journal of Neuroscience.

[28]  Michael J. O'Donovan,et al.  A Perimotor Framework Reveals Functional Segmentation in the Motoneuronal Network Controlling Locomotion in Caenorhabditis elegans , 2011, The Journal of Neuroscience.

[29]  Lav R. Varshney,et al.  Structural Properties of the Caenorhabditis elegans Neuronal Network , 2009, PLoS Comput. Biol..

[30]  S. Lockery,et al.  Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans. , 2011, Nature communications.

[31]  William S. Ryu,et al.  An Imbalancing Act: Gap Junctions Reduce the Backward Motor Circuit Activity to Bias C. elegans for Forward Locomotion , 2011, Neuron.

[32]  S. Lockery,et al.  An Image-Free Opto-Mechanical System for Creating Virtual Environments and Imaging Neuronal Activity in Freely Moving Caenorhabditis elegans , 2011, PloS one.

[33]  Aravinthan D. T. Samuel,et al.  Proprioceptive Coupling within Motor Neurons Drives C. elegans Forward Locomotion , 2012, Neuron.

[34]  Jordan H. Boyle,et al.  Gait Modulation in C. elegans: An Integrated Neuromechanical Model , 2012, Front. Comput. Neurosci..

[35]  Pascal Hersen,et al.  Locomotion control of Caenorhabditis elegans through confinement. , 2012, Biophysical journal.

[36]  Jun Zhang,et al.  Experiments and theory of undulatory locomotion in a simple structured medium , 2012, Journal of The Royal Society Interface.

[37]  Roger Y. Tsien,et al.  Photo-inducible cell ablation in Caenorhabditis elegans using the genetically encoded singlet oxygen generating protein miniSOG , 2012, Proceedings of the National Academy of Sciences.

[38]  Travis A. Jarrell,et al.  The Connectome of a Decision-Making Neural Network , 2012, Science.

[39]  P. Guertin Central Pattern Generator for Locomotion: Anatomical, Physiological, and Pathophysiological Considerations , 2013, Front. Neur..

[40]  Yi Wang,et al.  Computer Assisted Assembly of Connectomes from Electron Micrographs: Application to Caenorhabditis elegans , 2013, PloS one.

[41]  Randall D. Beer,et al.  Connecting a Connectome to Behavior: An Ensemble of Neuroanatomical Models of C. elegans Klinotaxis , 2013, PLoS Comput. Biol..

[42]  Paul W. Sternberg,et al.  Synaptic polarity of the interneuron circuit controlling C. elegans locomotion , 2013, Front. Comput. Neurosci..

[43]  N. Cohen,et al.  Nematode locomotion: dissecting the neuronal–environmental loop , 2014, Current Opinion in Neurobiology.

[44]  J. Gjorgjieva,et al.  Neurobiology of Caenorhabditis elegans Locomotion: Where Do We Stand? , 2014, Bioscience.

[45]  Theodore H. Lindsay,et al.  Global Brain Dynamics Embed the Motor Command Sequence of Caenorhabditis elegans , 2015, Cell.

[46]  Aravinthan D. T. Samuel,et al.  C. elegans locomotion: small circuits, complex functions , 2015, Current Opinion in Neurobiology.

[47]  Randall D. Beer,et al.  An Integrated Neuromechanical Model of Steering in C. elegans , 2015, ECAL.

[48]  Guoyin Wang,et al.  Biological modeling the undulatory locomotion of C. elegans using dynamic neural network approach , 2016, Neurocomputing.

[49]  Masahiro Kuramochi,et al.  A Computational Model Based on Multi-Regional Calcium Imaging Represents the Spatio-Temporal Dynamics in a Caenorhabditis elegans Sensory Neuron , 2017, PloS one.

[50]  Mark J Alkema,et al.  Excitatory Motor Neurons are Local Central Pattern Generators in an 1 Anatomically Compressed Motor Circuit for Reverse Locomotion 2 , 2017 .

[51]  Steven L. Brunton,et al.  Spatiotemporal Feedback and Network Structure Drive and Encode Caenorhabditis elegans Locomotion , 2017, PLoS Comput. Biol..

[52]  Michelle D. Po,et al.  A descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions , 2017, bioRxiv.

[53]  Michelle D. Po,et al.  Descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions , 2018, Proceedings of the National Academy of Sciences.

[54]  Eli J. Cornblath,et al.  Distributed rhythm generators underlie Caenorhabditis elegans forward locomotion , 2017, bioRxiv.

[55]  O. Sporns The connectome , 2020, New Oxford Textbook of Psychiatry.