Multisite regulation integrates multimodal context in sensory circuits to control persistent behavioral states in C. elegans

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 26, 2023

Abstract Maintaining or shifting between behavioral states according to context is essential for animals implement fitness-promoting strategies. How the integration of internal state, past experience and sensory inputs orchestrates persistent multidimensional changes remains poorly understood. Here, we show that C. elegans integrates environmental temperature food availability over different timescales engage in dwelling, scanning, global glocal search strategies matching thermoregulatory feeding needs. Transition states, each case, involves regulating multiple processes including AFD FLP tonic neurons activity, neuropeptide expression downstream circuit responsiveness. State-specific FLP-6 FLP-5 signaling acts on a distributed set inhibitory GPCR(s) promote scanning search, respectively, bypassing dopamine glutamate-dependent state control. Integration multimodal via multisite regulation circuits might represent conserved regulatory logic flexible prioritization valence when operating transitions.

Language: Английский

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The neuropeptidergic connectome ofC. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 31, 2022

Summary Efforts are currently ongoing to map synaptic wiring diagrams or connectomes in order understand the neural basis of brain function. However, chemical synapses represent only one type functionally important neuronal connection; particular, extrasynaptic, “wireless” signaling by neuropeptides is widespread and plays essential roles all nervous systems. By integrating single-cell anatomical gene expression datasets with a biochemical analysis receptor-ligand interactions, we have generated draft connectome neuropeptide C. elegans system. This characterized high connection density, extended cascades, autocrine foci, decentralized topology, large, highly interconnected core containing three constituent communities sharing similar patterns input connectivity. Intriguingly, several most nodes this little-studied neurons that specialized for peptidergic neuromodulation. We anticipate neuropeptidergic will serve as prototype basic organizational principles neuroendocrine networks.

Language: Английский

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Large-scale deorphanization of Nematostella vectensis neuropeptide G protein-coupled receptors supports the independent expansion of bilaterian and cnidarian peptidergic systems

eLife, Journal Year: 2024, Volume and Issue: 12

Published: May 10, 2024

Neuropeptides are ancient signaling molecules in animals but only few peptide receptors known outside bilaterians. Cnidarians possess a large number of G protein-coupled (GPCRs) – the most common bilaterian neuropeptides these remain orphan with no ligands. We searched for sea anemone Nematostella vectensis and created library 64 peptides derived from 33 precursors. In large-scale pharmacological screen 161 N. GPCRs, we identified 31 specifically activated by 1 to 3 14 peptides. Mapping GPCR neuropeptide expression single-cell sequencing data revealed how cnidarian tissues extensively connected multilayer peptidergic networks. Phylogenetic analysis direct orthology systems supports independent expansion cnidarians ancestral peptide-receptor pairs.

Language: Английский

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The Logic of Transgenerational Inheritance: Timescales of Adaptation

Annual Review of Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 39(1), P. 45 - 65

Published: June 20, 2023

Myriad mechanisms have evolved to adapt changing environments. Environmental stimuli alter organisms' physiology create memories of previous Whether these environmental can cross the generational barrier has interested scientists for centuries. The logic passing on information from generation is not well understood. When it useful remember ancestral conditions, and when might be deleterious continue respond a context that may no longer exist? key found in understanding conditions trigger long-lasting adaptive responses. We discuss biological systems use conditions. Responses spanning different timescales employ molecular machineries result differences duration or intensity exposure. Understanding components multigenerational inheritance underlying beneficial maladaptive adaptations fundamental how organisms acquire transmit across generations.

Language: Английский

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Pathogen infection induces sickness behaviors by recruiting neuromodulatory systems linked to stress and satiety inC. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 5, 2024

SUMMARY When animals are infected by a pathogen, peripheral sensors of infection signal to the brain coordinate set adaptive behavioral changes known as sickness behaviors. While pathways that from periphery have been intensively studied in recent years, how central circuits reconfigured elicit behaviors is not well understood. Here we find neuromodulatory systems linked stress and satiety recruited upon drive C. elegans . Upon chronic bacterium Pseudomonas aeruginosa PA14, decrease their feeding behavior, then display reversible bouts quiescence, eventually die. The ALA neuron its neuropeptides FLP-7, FLP-24, NLP-8, which control stress-induced sleep uninfected animals, promote PA14-induced reduction. However, neuropeptide FLP-13 instead acts delay quiescence death animals. Cell-specific genetic perturbations show neurons release distinct ALA. A brain-wide imaging screen reveals infection-induced involves ASI DAF-7/TGF-beta, satiety-induced Our results suggest common neuromodulators across different physiological states, acting neural sources combinations state-dependent

Language: Английский

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The head mesodermal cell couples FMRFamide neuropeptide signaling with rhythmic muscle contraction in C. elegans

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 14, 2023

Abstract FMRFamides are evolutionarily conserved neuropeptides that play critical roles in behavior, energy balance, and reproduction. Here, we show FMRFamide signaling from the nervous system is for rhythmic activation of a single cell previously unknown function, head mesodermal (hmc) C. elegans . Behavioral, calcium imaging, genetic studies reveal release FLP-22 neuropeptide AVL neuron response to pacemaker activates hmc every 50 s through an frpr-17 G protein-coupled receptor (GPCR) protein kinase A cascade hmc. results muscle contraction coupling by gap junctions composed UNC-9/Innexin. inhibited neuronal second FMRFamide-like neuropeptide, FLP-9, which functions its GPCR, frpr-21 , This study reveals function two opposing pathways controlling target volume transmission.

Language: Английский

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Large-scale deorphanization of Nematostella vectensis neuropeptide GPCRs supports the independent expansion of bilaterian and cnidarian peptidergic systems

Published: April 8, 2024

Neuropeptides are ancient signaling molecules in animals but only few peptide receptors known outside bilaterians. Cnidarians possess a large number of G protein-coupled (GPCRs) – the most common bilaterian neuropeptides these remain orphan with no ligands. We searched for sea anemone Nematostella vectensis and created library 64 peptides derived from 33 precursors. In large-scale pharmacological screen 161 N. GPCRs, we identified 31 specifically activated by one 14 peptides. Mapping GPCR neuropeptide expression to single-cell sequencing data revealed how cnidarian tissues extensively wired multilayer peptidergic networks. Phylogenetic analysis direct orthology systems supports independent expansion cnidarians ancestral peptide-receptor pairs.

Language: Английский

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Large-scale deorphanization of Nematostella vectensis neuropeptide G protein-coupled receptors supports the independent expansion of bilaterian and cnidarian peptidergic systems

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Sept. 29, 2023

Neuropeptides are ancient signaling molecules in animals but only few peptide receptors known outside bilaterians. Cnidarians possess a large number of G protein-coupled (GPCRs) – the most common bilaterian neuropeptides these remain orphan with no ligands. We searched for sea anemone Nematostella vectensis and created library 64 peptides derived from 33 precursors. In large-scale pharmacological screen 161 N. GPCRs, we identified 31 specifically activated by 1 to 3 14 peptides. Mapping GPCR neuropeptide expression single-cell sequencing data revealed how cnidarian tissues extensively connected multilayer peptidergic networks. Phylogenetic analysis direct orthology systems supports independent expansion cnidarians ancestral peptide-receptor pairs.

Language: Английский

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Scalable Apparatus to Measure Posture and Locomotion (SAMPL): a high-throughput solution to study unconstrained vertical behavior in small animals

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 7, 2023

Balance and movement are impaired in a wide variety of neurological disorders. Recent advances behavioral monitoring provide unprecedented access to posture locomotor kinematics, but without the throughput scalability necessary screen candidate genes / potential therapeutics. We present powerful solution: Scalable Apparatus Measure Posture Locomotion (SAMPL). SAMPL includes extensible imaging hardware low-cost open-source acquisition software with real-time processing. first demonstrate that SAMPL's can acquire data from D. melanogaster, C. elegans, rerio as they move vertically. Next, we leverage rapidly (two weeks) gather new zebrafish dataset. use analysis visualization tools replicate extend our current understanding how balance navigate through vertical environment. discover (1) key kinematic parameters vary systematically genetic background, (2) such background variation is small relative changes accompany early development. Finally, simulate ability resolve differences or navigation function affect size gathered -- for screens. Taken together, apparatus, data, solution labs using animals investigate disorders at scale. More broadly, both an adaptable resource looking process videographic measures behavior real-time, exemplar scale enable screening.

Language: Английский

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A single neuron inC. elegansorchestrates multiple motor outputs through parallel modes of transmission

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 2, 2023

Animals generate a wide range of highly coordinated motor outputs, which allows them to execute purposeful behaviors. Individual neuron classes in the circuits that behavior have remarkable capacity for flexibility, as they exhibit multiple axonal projections, transmitter systems, and modes neural activity. How these multi-functional properties neurons enable generation behaviors remains unknown. Here we show HSN

Language: Английский

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