Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics

To establish the relationship between locomotory behavior and dynamics of neural circuits in the nematode C. elegans we combined molecular and theoretical approaches. In particular, we quantitatively analyzed the motion of C. elegans with defective synaptic GABA and acetylcholine transmission, defective muscle calcium signaling, and defective muscles and cuticle structures, and compared the data with our systems level circuit model. The major experimental findings are: (i) anterior-to-posterior gradients of body bending flex for almost all strains both for forward and backward motion, and for neuronal mutants, also analogous weak gradients of undulatory frequency, (ii) existence of some form of neuromuscular (stretch receptor) feedback, (iii) invariance of neuromuscular wavelength, (iv) biphasic dependence of frequency on synaptic signaling, and (v) decrease of frequency with increase of the muscle time constant. Based on (i) we hypothesize that the Central Pattern Generator (CPG) is located in the head both for forward and backward motion. Points (i) and (ii) are the starting assumptions for our theoretical model, whose dynamical patterns are qualitatively insensitive to the details of the CPG design if stretch receptor feedback is sufficiently strong and slow. The model reveals that stretch receptor coupling in the body wall is critical for generation of the neuromuscular wave. Our model agrees with our behavioral data(iii), (iv), and (v), and with other pertinent published data, e.g., that frequency is an increasing function of muscle gap-junction coupling.Comment: Neural control of C. elegans motion with genetic perturbation

Information flow through a model of the C. elegans klinotaxis circuit

Understanding how information about external stimuli is transformed into behavior is one of the central goals of neuroscience. Here we characterize the information flow through a complete sensorimotor circuit: from stimulus, to sensory neurons, to interneurons, to motor neurons, to muscles, to motion. Specifically, we apply a recently developed framework for quantifying information flow to a previously published ensemble of models of salt klinotaxis in the nematode worm C. elegans. The models are grounded in the neuroanatomy and currently known neurophysiology of the worm. The unknown model parameters were optimized to reproduce the worm's behavior. Information flow analysis reveals several key principles underlying how the models operate: (1) Interneuron class AIY is responsible for integrating information about positive and negative changes in concentration, and exhibits a strong left/right information asymmetry. (2) Gap junctions play a crucial role in the transfer of information responsible for the information symmetry observed in interneuron class AIZ. (3) Neck motor neuron class SMB implements an information gating mechanism that underlies the circuit's state-dependent response. (4) The neck carries non-uniform distribution about changes in concentration. Thus, not all directions of movement are equally informative. Each of these findings corresponds to an experimental prediction that could be tested in the worm to greatly refine our understanding of the neural circuit underlying klinotaxis. Information flow analysis also allows us to explore how information flow relates to underlying electrophysiology. Despite large variations in the neural parameters of individual circuits, the overall information flow architecture circuit is remarkably consistent across the ensemble, suggesting that information flow analysis captures general principles of operation for the klinotaxis circuit

Modeling the chemotaxis behaviors of C. Elegans using neural network: from artificial to biological approach

Ph.DDOCTOR OF PHILOSOPH

Emulation of chemical stimulus triggered head movement in the C. elegans nematode

For a considerable time, it has been the goal of computational neuroscientists to understand biological nervous systems. However, the vast complexity of such systems has made it very difficult to fully understand even basic functions such as movement. Because of its small neuron count, the C. elegans nematode offers the opportunity to study a fully described connectome and attempt to link neural network activity to behaviour. In this paper a simulation of the neural network in C. elegans that responds to chemical stimulus is presented and a consequent realistic head movement demonstrated. An evolutionary algorithm (EA) has been utilised to search for estimates of the values of the synaptic conductances and also to determine whether each synapse is excitatory or inhibitory in nature. The chemotaxis neural network was designed and implemented, using the parameterization obtained with the EA, on the Si elegans platform a state-of-the-art hardware emulation platform specially designed to emulate the C. elegans nematode

Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain

Background: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. Methodology/Principal Findings: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. Conclusions/Significance: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological) motifs as long as both wiring and functional information is available

Bio-inspired robotic locomotion model: Response towards food gradient changes and temperature variation

The nervous system is a complex yet efficient structure - with superior information processing capabilities that surely surpass any man-made high-performance computer. Understanding this technology and utilising it in robotic navigation applications is essential to understand its underlying mechanism. One of the approaches is using a nematode’s biological network model, as having a simple network structure while holding a complex locomotion behaviour. For instance, its ability to navigate via local concentration cue (chemotaxis) and the ability to dynamically respond towards surrounding temperature (thermotaxis). To date, the simulation of currently available models is on static environment conditions and the nematode’s movement decision is based on the deterministic non-linear response towards gradient changes. Commonly, parameters of these models were optimised based on static conditions and require adjustment if simulated within a dynamic environment. Therefore, this work proposed a new nematode’s biological locomotion model where the movement trajectory is determined by the probability of “Run” and “Turn” signals. The model is simulated within a 2D virtual environment with complex concentration gradient and variants of temperature distribution. The analysis result shows the nematode’s movement of the proposed model agreed with the finding from experimental studies. Later, the proposed model in this work will be employed to develop a biological inspired multi-sensory robotic system for navigating within a dynamic and complex environmen