A neural circuit for navigation inspired by C. elegans Chemotaxis

We develop an artificial neural circuit for contour tracking and navigation inspired by the chemotaxis of the nematode Caenorhabditis elegans. In order to harness the computational advantages spiking neural networks promise over their non-spiking counterparts, we develop a network comprising 7-spiking neurons with non-plastic synapses which we show is extremely robust in tracking a range of concentrations. Our worm uses information regarding local temporal gradients in sodium chloride concentration to decide the instantaneous path for foraging, exploration and tracking. A key neuron pair in the C. elegans chemotaxis network is the ASEL & ASER neuron pair, which capture the gradient of concentration sensed by the worm in their graded membrane potentials. The primary sensory neurons for our network are a pair of artificial spiking neurons that function as gradient detectors whose design is adapted from a computational model of the ASE neuron pair in C. elegans. Simulations show that our worm is able to detect the set-point with approximately four times higher probability than the optimal memoryless Levy foraging model. We also show that our spiking neural network is much more efficient and noise-resilient while navigating and tracking a contour, as compared to an equivalent non-spiking network. We demonstrate that our model is extremely robust to noise and with slight modifications can be used for other practical applications such as obstacle avoidance. Our network model could also be extended for use in three-dimensional contour tracking or obstacle avoidance

Microbial light-activatable proton pumps as neuronal inhibitors to functionally dissect neuronal networks in C. elegans

Essentially any behavior in simple and complex animals depends on neuronal network function. Currently, the best-defined system to study neuronal circuits is the nematode Caenorhabditis elegans, as the connectivity of its 302 neurons is exactly known. Individual neurons can be activated by photostimulation of Channelrhodopsin-2 (ChR2) using blue light, allowing to directly probe the importance of a particular neuron for the respective behavioral output of the network under study. In analogy, other excitable cells can be inhibited by expressing Halorhodopsin from Natronomonas pharaonis (NpHR) and subsequent illumination with yellow light. However, inhibiting C. elegans neurons using NpHR is difficult. Recently, proton pumps from various sources were established as valuable alternative hyperpolarizers. Here we show that archaerhodopsin-3 (Arch) from Halorubrum sodomense and a proton pump from the fungus Leptosphaeria maculans (Mac) can be utilized to effectively inhibit excitable cells in C. elegans. Arch is the most powerful hyperpolarizer when illuminated with yellow or green light while the action spectrum of Mac is more blue-shifted, as analyzed by light-evoked behaviors and electrophysiology. This allows these tools to be combined in various ways with ChR2 to analyze different subsets of neurons within a circuit. We exemplify this by means of the polymodal aversive sensory ASH neurons, and the downstream command interneurons to which ASH neurons signal to trigger a reversal followed by a directional turn. Photostimulating ASH and subsequently inhibiting command interneurons using two-color illumination of different body segments, allows investigating temporal aspects of signaling downstream of ASH

Opportunities and challenges for modelling epidemiological and evolutionary dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in West Africa

Multihost multiparasite systems are evolutionarily and ecologically dynamic, which presents substantial trans‐disciplinary challenges for elucidating their epidemiology and designing appropriate control. Evidence for hybridizations and introgressions between parasite species is gathering, in part in line with improvements in molecular diagnostics and genome sequencing. One major system where this is becoming apparent is within the Genus Schistosoma, where schistosomiasis represents a disease of considerable medical and veterinary importance, the greatest burden of which occurs in sub‐Saharan Africa. Interspecific hybridizations and introgressions bring an increased level of complexity over and above that already inherent within multihost, multiparasite systems, also representing an additional source of genetic variation that can drive evolution. This has the potential for profound implications for the control of parasitic diseases, including, but not exclusive to, widening host range, increased transmission potential and altered responses to drug therapy. Here, we present the challenging case example of haematobium group Schistosoma spp. hybrids in West Africa, a system involving multiple interacting parasites and multiple definitive hosts, in a region where zoonotic reservoirs of schistosomiasis were not previously considered to be of importance. We consider how existing mathematical model frameworks for schistosome transmission could be expanded and adapted to zoonotic hybrid systems, exploring how such model frameworks can utilize molecular and epidemiological data, as well as the complexities and challenges this presents. We also highlight the opportunities and value such mathematical models could bring to this and a range of similar multihost, multi and cross‐hybridizing parasites systems in our changing world

Assessing motor-related phenotypes of Caenorhabditis elegans with the wide field-of-view nematode tracking platform

Caenorhabditis elegans is a valuable model organism in biomedical research that has led to major discoveries in the fields of neurodegeneration, cancer and aging. Because movement phenotypes are commonly used and represent strong indicators of C. elegans fitness, there is an increasing need to replace manual assessments of worm motility with automated measurements to increase throughput and minimize observer biases. Here, we provide a protocol for the implementation of the improved wide field-of-view nematode tracking platform (WF-NTP), which enables the simultaneous analysis of hundreds of worms with respect to multiple behavioral parameters. The protocol takes only a few hours to complete, excluding the time spent culturing C. elegans, and includes (i) experimental design and preparation of samples, (ii) data recording, (iii) software management with appropriate parameter choices and (iv) post-experimental data analysis. We compare the WF-NTP with other existing worm trackers, including those having high spatial resolution. The main benefits of WF-NTP relate to the high number of worms that can be assessed at the same time on a whole-plate basis and the number of phenotypes that can be screened for simultaneously

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

From cellular vulnerability to altered circuit activity:a systems biology approach to study amyotrophic lateral sclerosis

The devastating effects of the brain losing its ability to control voluntary body movement are illustrated by diseases such as amyotrophic lateral sclerosis (ALS) - where the nerve cells that allow the brain to effectively communicate with muscles are progressively lost. Most of the ALS research traditionally revolves around the affected nerve cells, known as motoneurons, and aims to rescue their decline in function. Motoneurons are however part of larger networks in the nervous system and constantly receive, process and transmit signals. Therefore, even the smallest alteration of a single motoneuron will likely leave a mark on its connecting neurons and vice versa. Could it be that solely targeting the function of diseased neurons has unexpected effects in an already (mal)adapted network? To mimic ALS, we used the worm Caenorhabditis elegans engineered to express the human gene TDP-43. Dysregulated TDP-43 is considered a uniform hallmark of ALS and its expression in C. elegans causes severe paralysis. By developing and combining numerous technology-driven, mostly unbiased screening approaches we show that TDP-43 impedes neuronal function and causes an imbalance between stimulatory and inhibitory signals in the motor circuit. While functional output of repressed motoneurons could be restored via modulation of their activity, these interventions did not result in improved locomotion. Rebalancing the derailed motor circuit dynamics by combining multiple treatments, however, effectively restored movement. Because of the high degree of similarity in genetic alterations and pathology between ALS worms and patients, similar therapeutic strategies may eventually be valuable for ALS patients