scholarly journals Neuroligin dependence of pharyngeal pumping reveals an extrapharyngeal modulation of Caenorhabditis elegans feeding

2018 ◽  
Author(s):  
Fernando Calahorro ◽  
Francesca Keefe ◽  
James Dillon ◽  
Lindy Holden-Dye ◽  
Vincent O’Connor
Keyword(s):  
Decision Making ◽  
Nervous System ◽  
Body Wall ◽  
Neural Circuits ◽  
Orthologous Gene ◽  
Sensory Cues ◽  
C Elegans ◽  
Sensory Modalities ◽  
Pharyngeal Pumping

ABSTRACTThe integration of distinct sensory modalities is essential for behavioural decision making. In C. elegans this process is coordinated by neural circuits that integrate sensory cues from the environment to generate an appropriate behaviour at the appropriate output muscles. Food is a multimodal cue that impacts on the microcircuits to modulating feeding and foraging drivers at the level of the pharyngeal and body wall muscle respectively. When food triggers an upregulation in pharyngeal pumping it allows the effective ingestion of food. Here we show that a C. elegans mutant in the single orthologous gene of human neuroligins, nlg-1 are defective in food induced pumping. This is not explained by an inability to sense food, as nlg-1 mutants are not defective in chemotaxis towards bacteria. In addition, we show that neuroligin is widely expressed in the nervous system including AIY, ADE, ALA, URX and HSN neurones. Interestingly, despite the deficit in pharyngeal pumping neuroligin is not expressed within the pharyngeal neuromuscular network, which suggests an extrapharyngeal regulation of this circuit. We resolve electrophysiologically the neuroligin contribution to the pharyngeal circuit by mimicking a food-dependent pumping, and show that the nlg-1 phenotype is similar to mutants impaired in GABAergic and/or glutamatergic signalling. We suggest that neuroligin organizes extrapharyngeal circuits that regulate the pharynx. These observations based on the molecular and cellular determinants of feeding are consistent with the emerging role of neuroligin in discretely impacting functional circuits underpinning complex behaviours.

scholarly journals A collective modulatory basis for multisensory integration in C. elegans

2018 ◽  
Author(s):  
Gareth Harris ◽  
Taihong Wu ◽  
Gaia Linfield ◽  
Myung-Kyu Choi ◽  
He Liu ◽  
...  
Keyword(s):  
Decision Making ◽  
Nervous System ◽  
Multisensory Integration ◽  
Multisensory Processing ◽  
Neurological Diseases ◽  
Sensory Information ◽  
Sensory Cues ◽  
C Elegans ◽  
Behavioral Decision ◽  
Integrated Response

AbstractIn the natural environment, animals often encounter multiple sensory cues that are simultaneously present. The nervous system integrates the relevant sensory information to generate behavioral responses that have adaptive values. However, the signal transduction pathways and the molecules that regulate integrated behavioral response to multiple sensory cues are not well defined. Here, we characterize a collective modulatory basis for a behavioral decision in C. elegans when the animal is presented with an attractive food source together with a repulsive odorant. We show that distributed neuronal components in the worm nervous system and several neuromodulators orchestrate the decision-making process, suggesting that various states and contexts may modulate the multisensory integration. Among these modulators, we identify a new function of a conserved TGF-β pathway that regulates the integrated decision by inhibiting the signaling from a set of central neurons. Interestingly, we find that a common set of modulators, including the TGF-β pathway, regulate the integrated response to the pairing of different foods and repellents. Together, our results provide insights into the modulatory signals regulating multisensory integration and reveal potential mechanistic basis for the complex pathology underlying defects in multisensory processing shared by common neurological diseases.Author SummaryThe present study characterizes the modulation of a behavioral decision in C. elegans when the worm is presented with a food lawn that is paired with a repulsive smell. We show that multiple sensory neurons and interneurons play roles in making the decision. We also identify several modulatory molecules that are essential for the integrated decision when the animal faces a choice between the cues of opposing valence. We further show that many of these factors, which often represent different states and contexts, are common for behavioral decisions that integrate sensory information from different types of foods and repellents. Overall, our results reveal a collective molecular and cellular basis for integration of simultaneously present attractive and repulsive cues to fine-tune decision-making.

scholarly journals Preconditioning of Caenorhabditis elegans to Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity

2020 ◽  
Author(s):  
Heather L. Bennett ◽  
Patrick D. McClanahan ◽  
Christopher Fang-Yen ◽  
Robert G. Kalb
Keyword(s):  
Nervous System ◽  
Chloride Channels ◽  
Body Wall ◽  
Molecular Mechanisms ◽  
Oxygen Deprivation ◽  
C Elegans ◽  
Cell Dysfunction ◽  
Sublethal Stress ◽  
Body Wall Muscles

AbstractFor most metazoans, oxygen deprivation leads to cell dysfunction and if severe, death. Sublethal stress prior to a hypoxic or anoxic insult (“preconditioning”) can protect cells from subsequent oxygen deprivation. The molecular mechanisms by which sublethal stress can buffer against a subsequent toxic insult and the role of the nervous system in the response are not well understood. We studied the role of neuronal activity preconditioning to oxygen deprivation in C. elegans. Animals expressing the histamine gated chloride channels (HisCl1) in select cell populations were used to temporally and spatially inactivate the nervous system or tissue prior to an anoxic insult. We find that inactivation of the nervous system for 3 hours prior to the insult confers resistance to a 48-hour anoxic insult in 4th-stage larval animals. Experiments show that this resistance can be attributed to loss of activity in cholinergic and GABAergic neurons as well as in body wall muscles. These observations indicate that the nervous system activity can mediate the organism’s response to anoxia.

scholarly journals Novel Technological Advances in Functional Connectomics in C. elegans

2019 ◽  
Vol 7 (2) ◽  
pp. 8 ◽  
Author(s):  
DiLoreto ◽  
Chute ◽  
Bryce ◽  
Srinivasan
Keyword(s):  
Nervous System ◽  
Computational Modeling ◽  
Activity Patterns ◽  
Sensory Information ◽  
Neuronal Cell ◽  
Network Models ◽  
Connectivity Matrix ◽  
C Elegans ◽  
Technological Advances

The complete structure and connectivity of the Caenorhabditis elegans nervous system (“mind of a worm”) was first published in 1986, representing a critical milestone in the field of connectomics. The reconstruction of the nervous system (connectome) at the level of synapses provided a unique perspective of understanding how behavior can be coded within the nervous system. The following decades have seen the development of technologies that help understand how neural activity patterns are connected to behavior and modulated by sensory input. Investigations on the developmental origins of the connectome highlight the importance of role of neuronal cell lineages in the final connectivity matrix of the nervous system. Computational modeling of neuronal dynamics not only helps reconstruct the biophysical properties of individual neurons but also allows for subsequent reconstruction of whole-organism neuronal network models. Hence, combining experimental datasets with theoretical modeling of neurons generates a better understanding of organismal behavior. This review discusses some recent technological advances used to analyze and perturb whole-organism neuronal function along with developments in computational modeling, which allows for interrogation of both local and global neural circuits, leading to different behaviors. Combining these approaches will shed light into how neural networks process sensory information to generate the appropriate behavioral output, providing a complete understanding of the worm nervous system.

scholarly journals Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

2020 ◽  
Vol 21 (7) ◽  
pp. 2273
Author(s):  
Eunyoung Jung ◽  
Seong-Ho Koh ◽  
Myeongjong Yoo ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Carbon Monoxide ◽  
Nervous System ◽  
Neurotrophic Factors ◽  
Neural Circuits ◽  
Cns Injury ◽  
Cns Regeneration ◽  
The Central Nervous System ◽  
Endogenous Neural Stem Cells

Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer’s disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury.

scholarly journals Short-term hyperglycaemia induces motor defects in C. elegans

2017 ◽  
Author(s):  
Runita Shirdhankar ◽  
Nabila Sorathia ◽  
Medha Rajyadhyaksha
Keyword(s):  
Nervous System ◽  
Sensory Function ◽  
Motor Behaviour ◽  
Response Index ◽  
C Elegans ◽  
Cellular Effects ◽  
Pharyngeal Pumping ◽  
Intracellular Changes ◽  
Behaviour Study ◽  
Chemosensory Systems

AbstractHyperglycaemia causes various intracellular changes resulting in oxidative stress leading to loss of integrity and cell death. While cellular effects of hyperglycaemia have been reported extensively there is no clarity on whether the cellular changes translate into alterations in behaviour. Study of behavioural alterations also provides a sublime top-down approach to dapple the putative systems affected due to hyperglycaemic stress. Hence, this aspect of effect of hyperglycaemia deserves attention as it could be an early indicator of neurodegenerative changes. Caenorhabditis elegans is an excellent model to address these questions since it has a simple nervous system and the ability to respond to various cues.We have investigated alteration in behaviour which involves various motor and sensory function of the C. elegans nervous system under hyperglycaemia. Exposure of C. elegans to 400 mM glucose for 4hr did not kill the worm but gave rise to decreased number of progeny, exhibiting other aberrant behaviours. This dosage was considered to cause hyperglycaemic stress and used further in the studies. Various assays that quantified behaviour, such as feeding (pharyngeal pumping/min), locomotion (distance travelled by the worms/min), olfactory response towards Butanol (response index) and gustatory response NaCl (response index) were conducted under both normal and hyperglycaemic conditions. The behavioural alterations were validated by scrutinizing changes in level of Acetylchloine which regulates motor behaviour and morphology of chemosensory neurons. Our results indicate that hyperglycaemia alters motor behaviour of the worm which was validated by a reduction in ACh levels. However, chemosensory systems were robust enough to resist reduction in neuronal integrity due to hyperglycaemic assault.

scholarly journals Inhibition underlies fast undulatory locomotion in C. elegans

2020 ◽  
Author(s):  
Lan Deng ◽  
Jack Denham ◽  
Charu Arya ◽  
Omer Yuval ◽  
Netta Cohen ◽  
...  
Keyword(s):  
Computational Models ◽  
Body Wall ◽  
Activity Patterns ◽  
Wild Type ◽  
C Elegans ◽  
Body Wall Muscles ◽  
Undulatory Locomotion ◽  
Gaba Transmission ◽  
Cross Inhibition

AbstractInhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contraction of antagonist muscles, whether along the body axis or within and among limbs. In the nematode C. elegans, a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be necessary for backward undulation because mutants that are defective in GABA transmission exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited by wild-type as well as mutant animals in response to harsh touch to the head or tail, but only GABA transmission mutants show slow locomotion after stimulation. Impairment of GABA transmission, either genetically or optogenetically, induces lower undulation frequency and lower translocation speed during crawling and swimming in both directions. The activity patterns of GABAergic motoneurons are different during low and high undulation frequencies. During low undulation frequency, GABAergic VD and DD motoneurons show similar activity patterns, while during high undulation frequency, their activity alternates. The experimental results suggest at least three non-mutually exclusive roles for inhibition that could underlie fast undulatory locomotion in C. elegans, which we tested with computational models: cross-inhibition or disinhibition of body-wall muscles, or inhibitory reset.Significance StatementInhibition serves multiple roles in the generation, maintenance, and modulation of the locomotive program and supports the alternating activation of antagonistic muscles. When the locomotor frequency increases, more inhibition is required. To better understand the role of inhibition in locomotion, we used C. elegans as an animal model, and challenged a prevalent hypothesis that cross-inhibition supports the dorsoventral alternation. We find that inhibition is related to the speed rather than the direction of locomotion and demonstrate that inhibition is unnecessary for muscle alternation during slow undulation in either direction but crucial to sustain rapid dorsoventral alternation. We combined calcium imaging of motoneurons and muscle with computational models to test hypotheses for the role of inhibition in locomotion.

scholarly journals Cholinergic signalling at the body wall neuromuscular junction couples to distal inhibition of feeding in C. elegans

2021 ◽  
Author(s):  
Patricia G. Izquierdo ◽  
Thibana Thisainathan ◽  
James H. Atkins ◽  
Christian J. Lewis ◽  
John E.H. Tattersall ◽  
...  
Keyword(s):  
Body Wall ◽  
Neuromuscular Junctions ◽  
Model Organism ◽  
Inhibitory Effect ◽  
The Body ◽  
Body Wall Muscle ◽  
Cholinergic Transmission ◽  
Systematic Screening ◽  
C Elegans ◽  
Pharyngeal Pumping

AbstractComplex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organism C. elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. These distinct tissues are controlled by separate, well-defined neural circuits. Nonetheless, the emergent behaviours, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. We show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behaviour. This was evidenced by a systematic screening of the cholinesterase inhibitor aldicarb’s effect on the rate of pharyngeal pumping on food in mutant worms. The screening revealed that the key determinant of the inhibitory effect of aldicarb on pharyngeal pumping is the L-type nicotinic acetylcholine receptor expressed in body wall muscle. This idea was reinforced by the observation that selective hyperstimulation of the body wall muscle L-type receptor by the agonist levamisole inhibited pumping. Overall, our results reveal that body wall cholinergic transmission controls locomotion and simultaneously couples a distal inhibition of feeding.

scholarly journals Synthetic ablations in the C. elegans nervous system

2020 ◽  
Vol 4 (1) ◽  
pp. 200-216 ◽  
Author(s):  
Emma K. Towlson ◽  
Albert-László Barabási
Keyword(s):  
Nervous System ◽  
Synthetic Lethality ◽  
Neural System ◽  
Network Control ◽  
Loss Of Control ◽  
C Elegans ◽  
Touch Response ◽  
Systematic Framework ◽  
Systematic Knowledge

Synthetic lethality, the finding that the simultaneous knockout of two or more individually nonessential genes leads to cell or organism death, has offered a systematic framework to explore cellular function, and also offered therapeutic applications. Yet the concept lacks its parallel in neuroscience—a systematic knowledge base on the role of double or higher order ablations in the functioning of a neural system. Here, we use the framework of network control to systematically predict the effects of ablating neuron pairs and triplets on the gentle touch response. We find that surprisingly small sets of 58 pairs and 46 triplets can reduce muscle controllability in this context, and that these sets are localized in the nervous system in distinct groups. Further, they lead to highly specific experimentally testable predictions about mechanisms of loss of control, and which muscle cells are expected to experience this loss.

scholarly journals GABAergic motor neurons bias locomotor decision-making in C. elegans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ping Liu ◽  
Bojun Chen ◽  
Zhao-Wen Wang
Keyword(s):  
Decision Making ◽  
Motor Neurons ◽  
Gaba Receptor ◽  
Single Neuron ◽  
Neural Circuit ◽  
Electrical Coupling ◽  
C Elegans ◽  
Sensory Modalities ◽  
Motor Information ◽  
Molecular Bases

Abstract Proper threat-reward decision-making is critical to animal survival. Emerging evidence indicates that the motor system may participate in decision-making but the neural circuit and molecular bases for these functions are little known. We found in C. elegans that GABAergic motor neurons (D-MNs) bias toward the reward behavior in threat-reward decision-making by retrogradely inhibiting a pair of premotor command interneurons, AVA, that control cholinergic motor neurons in the avoidance neural circuit. This function of D-MNs is mediated by a specific ionotropic GABA receptor (UNC-49) in AVA, and depends on electrical coupling between the two AVA interneurons. Our results suggest that AVA are hub neurons where sensory inputs from threat and reward sensory modalities and motor information from D-MNs are integrated. This study demonstrates at single-neuron resolution how motor neurons may help shape threat-reward choice behaviors through interacting with other neurons.

Perceptual recalibration in sensory substitution and perceptual modification

2005 ◽  
Vol 13 (3) ◽  
pp. 481-500 ◽  
Author(s):  
Juan C. González ◽  
Paul Bach-y-Rita ◽  
Steven J. Haase
Keyword(s):  
Nervous System ◽  
Adaptive Capacity ◽  
Spatial Perception ◽  
Sensory Substitution ◽  
Dynamic Character ◽  
Sensory Modalities ◽  
Theoretical Issues

This paper analyzes the process of perceptual recalibration (PR) in light of two cases of technologically-mediated cognition: sensory substitution and perceptual modification. We hold that PR is a very useful concept — perhaps necessary — for explaining the adaptive capacity that natural perceptive systems display as they respond to functional demands from the environment. We also survey critically related issues, such as the role of learning, training, and nervous system plasticity in the recalibrating process. Attention is given to the interaction between technology and cognition, and the case of epistemic prostheses is presented as an illustration. Finally, we address the following theoretical issues: (1) the dynamic character of spatial perception; (2) the role of functional demands in perception; (3) the nature and interaction of sensory modalities. We aim to show that these issues may be addressed empirically and conceptually — hence, the usefulness of sensory-substitution and perceptual-modification studies in the analysis of perception, technologically-mediated cognition, and cognition in general.

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