scholarly journals Neural mechanisms driving hunger-induced changes in sensory perception and behavior in Caenorhabditis elegans

2017 ◽  
Author(s):  
Hiu E. Lau ◽  
Zachary T. Cecere ◽  
Zheng Liu ◽  
Claire J. Yang ◽  
Tatyana O. Sharpee ◽  
...  
Keyword(s):  
Internal State ◽  
Sensory Perception ◽  
Neuronal Dynamics ◽  
C Elegans ◽  
Appetitive Behavior ◽  
Internal States ◽  
Body Wall Muscles ◽  
Peptide Signals ◽  
Induced Changes ◽  
And Behavior

SummaryWhile much is known about how external cues affect neural circuits, less is known about how internal states modify their function. We acutely food-deprived C. elegans and analyzed its responses in integrating attractant and repellent signals. We show that food deprivation leads to a reversible decline in repellent sensitivity; with no effect on appetitive behavior allowing animals to engage in higher risk behavior. Multiple tissues including the intestine and body wall muscles use a conserved transcription factor, MondoA, to detect the lack of food and release AEX-5 convertase processed peptides from dense core vesicles. Subsequently, ASI chemosensory neurons use the DAF-2 insulin receptor and non-canonical signaling to integrate the tissue-released peptide signals modifying their stimulus-evoked adaptation rate. We suggest that altering ASI neuronal dynamics affects its function and modifies behavior. Together, these studies show how internal state signals modify sensory perception and risk assessment to generate flexible behaviors.

scholarly journals INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans

2019 ◽  
Author(s):  
Lisa Voelker ◽  
Bishal Upadhyaya ◽  
Denise M. Ferkey ◽  
Sarah Woldemariam ◽  
Noelle D. L’Etoile ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Internal State ◽  
Nerve Ring ◽  
Electrical Synapse ◽  
Electrical Synapses ◽  
C Elegans ◽  
Internal States ◽  
Sensory Responses ◽  
Aversive Behavior ◽  
Sites Of Action

AbstractIn order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize to different regions of the nerve ring, indicating that they are not present in the same synapses. Second, removing inx-18 disrupts the distribution of INX-19, while removing inx-19 does not alter INX-18 localization. Finally, by using a fluorescent cGMP reporter, we find that INX-18 and INX-19 have distinct roles in establishing cGMP levels in ASK and ASH. Together, these results demonstrate that electrical synapses containing INX-18 and INX-19 facilitate modulation of ASH nociceptive signaling. Our findings support the idea that a network of electrical synapses mediates cGMP exchange between neurons, enabling modulation of sensory responses and behavior.Author SummaryAnimals are constantly adjusting their behavior to respond to changes in the environment or to their internal state. This behavior modulation is achieved by altering the activity of neurons and circuits through a variety of neuroplasticity mechanisms. Chemical synapses are known to impact neuroplasticity in several different ways, but the diversity of mechanisms by which electrical synapses contribute is still being investigated. Electrical synapses are specialized sites of connection between neurons where ions and small signaling molecules can pass directly from one cell to the next. By passing small molecules through electrical synapses, neurons may be able to modify the activity of their neighbors. In this study we identify two genes that contribute to electrical synapses between two sensory neurons in C. elegans. We show that these electrical synapses are crucial for proper modulation of sensory responses, as without them animals are overly responsive to an aversive stimulus. In addition to pinpointing their sites of action, we present evidence that they may be contributing to neuromodulation by facilitating passage of the small molecule cGMP between neurons. Our work provides evidence for a role of electrical synapses in regulating animal behavior.

scholarly journals Learning is shaped by abrupt changes in neural engagement

2020 ◽  
Author(s):  
Jay A. Hennig ◽  
Emily R. Oby ◽  
Matthew D. Golub ◽  
Lindsay A. Bahureksa ◽  
Patrick T. Sadtler ◽  
...  
Keyword(s):  
Neural Activity ◽  
Internal State ◽  
Neural Population ◽  
Behavioral Performance ◽  
Population Activity ◽  
Large Fluctuations ◽  
Abrupt Changes ◽  
Internal States ◽  
Task Goals ◽  
And Behavior

AbstractInternal states such as arousal, attention, and motivation are known to modulate brain-wide neural activity, but how these processes interact with learning is not well understood. During learning, the brain must modify the neural activity it produces to improve behavioral performance. How do internal states affect the evolution of this learning process? Using a brain-computer interface (BCI) learning paradigm in non-human primates, we identified large fluctuations in neural population activity in motor cortex (M1) indicative of arousal-like internal state changes. These fluctuations drove population activity along dimensions we term neural engagement axes. Neural engagement increased abruptly at the start of learning, and then gradually retreated. In a BCI, the causal relationship between neural activity and behavior is known. This allowed us to understand how these changes impacted behavioral performance for different task goals. We found that neural engagement interacted with learning, helping to explain why animals learned some task goals more quickly than others.

scholarly journals Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

2021 ◽  
pp. 074873042098732
Author(s):  
N. Kronfeld-Schor ◽  
T. J. Stevenson ◽  
S. Nickbakhsh ◽  
E. S. Schernhammer ◽  
X. C. Dopico ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Multidisciplinary Approach ◽  
Preliminary Assessment ◽  
Epidemiological Evidence ◽  
Wide Range ◽  
Human Coronaviruses ◽  
Induced Changes ◽  
And Behavior ◽  
Timing Phase

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

Impaired discrimination of a subanesthetic dose of ketamine in a maternal immune activation model of schizophrenia risk

2021 ◽  
pp. 026988112110297
Author(s):  
Wayne Meighan ◽  
Thomas W Elston ◽  
David Bilkey ◽  
Ryan D Ward
Keyword(s):  
Animal Models ◽  
Drug Discrimination ◽  
Immune Activation ◽  
Internal State ◽  
Nmda Receptor Antagonist ◽  
Activation Model ◽  
Data Link ◽  
Maternal Immune Activation ◽  
Internal States ◽  
Reliable Methods

Background: Animal models of psychiatric diseases suffer from a lack of reliable methods for accurate assessment of subjective internal states in nonhumans. This gap makes translation of results from animal models to patients particularly challenging. Aims/methods: Here, we used the drug-discrimination paradigm to allow rats that model a risk factor for schizophrenia (maternal immune activation, MIA) to report on the subjective internal state produced by a subanesthetic dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. Results/outcomes: The MIA rats’ discrimination of ketamine was impaired relative to controls, both in the total number of rats that acquired and the asymptotic level of discrimination accuracy. This deficit was not due to a general inability to learn to discriminate an internal drug cue or internal state generally, as MIA rats were unimpaired in the learning and acquisition of a morphine drug discrimination and were as sensitive to the internal state of satiety as controls. Furthermore, the deficit was not due to a decreased sensitivity to the physiological effects of ketamine, as MIA rats showed increased ketamine-induced locomotor activity. Finally, impaired discrimination of ketamine was only seen at subanesthetic doses which functionally correspond to psychotomimetic doses in humans. Conclusion: These data link changes in NMDA responses to the MIA model. Furthermore, they confirm the utility of the drug-discrimination paradigm for future inquiries into the subjective internal state produced in models of schizophrenia and other developmental diseases.

scholarly journals Hydrogen Sulfide Increases Hypoxia-inducible Factor-1 Activity Independently of von Hippel–Lindau Tumor Suppressor-1 inC. elegans

2010 ◽  
Vol 21 (1) ◽  
pp. 212-217 ◽  
Author(s):  
Mark W. Budde ◽  
Mark B. Roth
Keyword(s):  
Hydrogen Sulfide ◽  
Tumor Suppressor ◽  
Environmental Changes ◽  
Hypoxia Inducible Factor ◽  
Low Oxygen ◽  
Animal Cells ◽  
Von Hippel Lindau ◽  
C Elegans ◽  
Reporter Activity ◽  
And Behavior

Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor hypoxia-inducible factor (HIF)-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H2S). Here, we show that Caenorhabditis elegans can have mutually exclusive responses to H2S and hypoxia, both involving HIF-1. Specifically, H2S results in HIF-1 activity throughout the hypodermis, whereas hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. C. elegans require hif-1 to survive in room air containing trace amounts of H2S. Exposure to H2S results in HIF-1 nuclear localization and transcription of HIF-1 targets. The effects of H2S on HIF-1 reporter activity are independent of von Hippel–Lindau tumor suppressor (VHL)-1, whereas VHL-1 is required for hypoxic regulation of HIF-1 reporter activity. Because H2S is naturally produced by animal cells, our results suggest that endogenous H2S may influence HIF-1 activity.

scholarly journals Autonomous Decision-Making While Drilling

Energies ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 969
Author(s):  
Eric Cayeux ◽  
Benoît Daireaux ◽  
Adrian Ambrus ◽  
Rodica Mihai ◽  
Liv Carlsen
Keyword(s):  
Decision Making ◽  
Internal State ◽  
Drilling Process ◽  
Autonomous Decision ◽  
Internal States ◽  
Markov Decision ◽  
Drilling Operations ◽  
Drilling System ◽  
Drilling Conditions ◽  
Erratic Behavior

The drilling process is complex because unexpected situations may occur at any time. Furthermore, the drilling system is extremely long and slender, therefore prone to vibrations and often being dominated by long transient periods. Adding the fact that measurements are not well distributed along the drilling system, with the majority of real-time measurements only available at the top side and having only access to very sparse data from downhole, the drilling process is poorly observed therefore making it difficult to use standard control methods. Therefore, to achieve completely autonomous drilling operations, it is necessary to utilize a method that is capable of estimating the internal state of the drilling system from parsimonious information while being able to make decisions that will keep the operation safe but effective. A solution enabling autonomous decision-making while drilling has been developed. It relies on an optimization of the time to reach the section total depth (TD). The estimated time to reach the section TD is decomposed into the effective time spent in conducting the drilling operation and the likely time lost to solve unexpected drilling events. This optimization problem is solved by using a Markov decision process method. Several example scenarios have been run in a virtual rig environment to test the validity of the concept. It is found that the system is capable to adapt itself to various drilling conditions, as for example being aggressive when the operation runs smoothly and the estimated uncertainty of the internal states is low, but also more cautious when the downhole drilling conditions deteriorate or when observations tend to indicate more erratic behavior, which is often observed prior to a drilling event.

scholarly journals Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

2016 ◽  
Vol 113 (36) ◽  
pp. 10055-10060 ◽  
Author(s):  
Xinxing Zhang ◽  
Kunhua Li ◽  
Rachel A. Jones ◽  
Steven D. Bruner ◽  
Rebecca A. Butcher
Keyword(s):  
Caenorhabditis Elegans ◽  
Nematode Species ◽  
Binding Pocket ◽  
Pheromone Biosynthesis ◽  
Atp Binding ◽  
Metabolic State ◽  
C Elegans ◽  
Acyl Coa Oxidase ◽  
Key Residues ◽  
And Behavior

Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state.

Positioning and maintenance of embryonic body wall muscle attachments in C. elegans requires the mup-1 gene

Development ◽  
1991 ◽  
Vol 111 (3) ◽  
pp. 667-681 ◽  
Author(s):  
P.Y. Goh ◽  
T. Bogaert
Keyword(s):  
Extracellular Matrix ◽  
Body Wall ◽  
Early Stage ◽  
Muscle Growth ◽  
The Body ◽  
Body Wall Muscle ◽  
C Elegans ◽  
Extracellular Matrix Molecule ◽  
Extracellular Matrix Components ◽  
Body Wall Muscles

As part of a general study of genes specifying a pattern of muscle attachments, we identified and genetically characterised mutants in the mup-1 gene. The body wall muscles of early stage mup-1 embryos have a wild-type myofilament pattern but may extend ectopic processes. Later in embryogenesis, some body wall muscles detach from the hypodermis. Genetic analysis suggests that mup-1 has both a maternal and a zygotic component and is not required for postembryonic muscle growth and attachment. mup-1 mutants are suppressed by mutations in several genes that encode extracellular matrix components. We propose that mup-1 may encode a cell surface/extracellular matrix molecule required both for the positioning of body wall muscle attachments in early embryogenesis and the subsequent maintenance of these attachments to the hypodermis until after cuticle synthesis.

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