scholarly journals MALT1 mediates IL-17 Neural Signaling to regulate C. elegans behavior, immunity and longevity

2019 ◽  
Author(s):  
Sean M. Flynn ◽  
Changchun Chen ◽  
Murat Artan ◽  
Stephen Barratt ◽  
Alastair Crisp ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Circuit ◽  
Escape Behavior ◽  
Interleukin 17 ◽  
Neural Function ◽  
Behavioral State ◽  
C Elegans ◽  
Nervous System Function ◽  
Circuit Function ◽  
Neural Signaling

AbstractBesides well-known immune roles, the evolutionarily ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate how IL-17 signals in neurons, and the extent to which this signaling can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans (Ce) neurons. We identify the Ce ortholog of MALT1 as a critical output of the pathway. MALT1 was not previously implicated in IL-17 signaling or in nervous system function. MALT1 forms a complex with homologs of Act1 and IRAK and functions both as a scaffold for IκB recruitment, and as a protease. MALT1 is expressed broadly in the Ce nervous system, and neuronal IL-17–MALT1 signaling regulates many phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural function downstream of IL-17 to remodel physiological and behavioral state.

Myelin Plasticity and Nervous System Function

2018 ◽  
Vol 41 (1) ◽  
pp. 61-76 ◽  
Author(s):  
Michelle Monje
Keyword(s):  
Nervous System ◽  
Neural Circuit ◽  
Neurological Function ◽  
Nervous System Activity ◽  
Second Mode ◽  
Nervous System Function ◽  
Plastic Changes ◽  
Circuit Function ◽  
Activity Dependent ◽  
Development Proceeds

Structural plasticity in the myelinated infrastructure of the nervous system has come to light. Although an innate program of myelin development proceeds independent of nervous system activity, a second mode of myelination exists in which activity-dependent, plastic changes in myelin-forming cells influence myelin structure and neurological function. These complementary and possibly temporally overlapping activity-independent and activity-dependent modes of myelination crystallize in a model of experience-modulated myelin development and plasticity with broad implications for neurological function. In this article, I consider the contributions of myelin to neural circuit function, the dynamic influences of experience on myelin microstructure, and the role that plasticity of myelin may play in cognition.

scholarly journals Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

2021 ◽  
Vol 14 ◽  
Author(s):  
Umer Saleem Bhat ◽  
Navneet Shahi ◽  
Siju Surendran ◽  
Kavita Babu
Keyword(s):  
Nervous System ◽  
Behavioral Plasticity ◽  
Environmental Changes ◽  
Sensory Information ◽  
Synaptic Activity ◽  
Small Peptides ◽  
C Elegans ◽  
Wide Range ◽  
Nervous System Function ◽  
Insight Into

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

scholarly journals Neural architecture: from cells to circuits

2018 ◽  
Vol 120 (2) ◽  
pp. 854-866 ◽  
Author(s):  
Sarah E. V. Richards ◽  
Stephen D. Van Hooser
Keyword(s):  
Nervous System ◽  
Cerebral Cortex ◽  
Structure Function ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neuronal Morphology ◽  
Neural Architecture ◽  
Synaptic Interactions ◽  
Branching Patterns ◽  
Circuit Function

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.

scholarly journals Neuroendocrine Modulation Sustains the C. elegans Forward Motor State

2016 ◽  
Author(s):  
Maria A. Lim ◽  
Jyothsna Chitturi ◽  
Valeriya Laskova ◽  
Jun Meng ◽  
Daniel Findeis ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Transcriptome Profiling ◽  
Behavioral State ◽  
Forward Movement ◽  
C Elegans ◽  
Peptidergic Neuron ◽  
Homeobox Transcription Factor

AbstractNeuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

scholarly journals Decoding a neural circuit controlling global animal state in C. elegans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Patrick Laurent ◽  
Zoltan Soltesz ◽  
Geoffrey M Nelson ◽  
Changchun Chen ◽  
Fausto Arellano-Carbajal ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Neural Circuit ◽  
Behavioral State ◽  
Global State ◽  
C Elegans ◽  
Neural Imaging ◽  
Neural Genes ◽  
O2 Concentration ◽  
High O2 ◽  
O2 Sensing

Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.

scholarly journals A cellular and regulatory map of the GABAergic nervous system of C. elegans

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Marie Gendrel ◽  
Emily G Atlas ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Gaba Receptors ◽  
Cholinergic Neurons ◽  
Transcriptional Regulators ◽  
Comprehensive Analysis ◽  
Gaba Uptake ◽  
C Elegans ◽  
Positive Neuron ◽  
Nervous System Function ◽  
Extracellular Environment

Neurotransmitter maps are important complements to anatomical maps and represent an invaluable resource to understand nervous system function and development. We report here a comprehensive map of neurons in the C. elegans nervous system that contain the neurotransmitter GABA, revealing twice as many GABA-positive neuron classes as previously reported. We define previously unknown glia-like cells that take up GABA, as well as 'GABA uptake neurons' which do not synthesize GABA but take it up from the extracellular environment, and we map the expression of previously uncharacterized ionotropic GABA receptors. We use the map of GABA-positive neurons for a comprehensive analysis of transcriptional regulators that define the GABA phenotype. We synthesize our findings of specification of GABAergic neurons with previous reports on the specification of glutamatergic and cholinergic neurons into a nervous system-wide regulatory map which defines neurotransmitter specification mechanisms for more than half of all neuron classes in C. elegans.

scholarly journals The Emergent Connectome in Caenorhabditis elegans Embryogenesis

2017 ◽  
Author(s):  
◽  
Bradly Alicea
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Cell Lineage ◽  
Model Organism ◽  
Secondary Data ◽  
Building Blocks ◽  
C Elegans ◽  
Differentiated Cells ◽  
Adult Hermaphrodite ◽  
Nervous System Function

ABSTRACTThe relatively new field of connectomics provides us with a unique window into nervous system function. In the model organism Caenorhabditis elegans, this promise is even greater due to the relatively small number of cells (302) in its nervous system. While the adult C. elegans connectome has been characterized, the emergence of these networks in development has yet to be established. In this paper, we approach this problem using secondary data describing the birth times of terminally-differentiated cells as they appear in the embryo and a connectomics model for nervous system cells in the adult hermaphrodite. By combining these two sources of data, we can better understand patterns that emerge in an incipient connectome. This includes identifying at what point in embryogenesis the cells of a connectome first comes into being, potentially observing some of the earliest neuron-neuron interactions, and making comparisons between the formally-defined connectome and developmental cell lineages. An analysis is also conducted to root terminally-differentiated cells in their developmental cell lineage precursors. This reveals subnetworks with different properties at 300 minutes of embryogenesis. Additional investigations reveal the spatial position of neuronal cells born during pre-hatch development, both within and outside the connectome model, in the context of all developmental cells in the embryo. Overall, these analyses reveal important information about the birth order of specific cells in the connectome, key building blocks of global connectivity, and how these structures correspond to key events in early development.

scholarly journals Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans

2017 ◽  
Author(s):  
Michael P. O’Donnell ◽  
Pin-Hao Chao ◽  
Jan E. Kammenga ◽  
Piali Sengupta
Keyword(s):  
Nervous System ◽  
Internal State ◽  
Environmental Signals ◽  
C Elegans ◽  
Signaling Complex ◽  
External Cues ◽  
Nervous System Function ◽  
Sensory Nervous System ◽  
Neuronal Functions ◽  
Available Information

ABSTRACTAnimals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematode C. elegans. During development, pheromone, bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 insulin-like peptide in sensory neurons to promote a binary decision between reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which together reflect bacterial-diet dependent feeding status, thus providing a mechanism for integration of food signals with external cues in the regulation of neuroendocrine gene expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated foraging behaviors via the PDFR-1 neuropeptide receptor. We also demonstrate that genetic variation affects food-dependent larval and adult phenotypes, and identify quantitative trait loci (QTL) associated with these traits.Together, these results suggest that TORC2 acts as a hub for communication of feeding state information from the gut to the brain, thereby contributing to modulation of neuronal function by internal state.AUTHOR SUMMARYDecision-making in all animals, including humans, involves weighing available information about the external environment as well as the animals’ internal conditions. Information about the environment is obtained via the sensory nervous system, whereas internal state can be assessed via cues such as levels of hormones or nutrients. How multiple external and internal inputs are processed in the nervous system to drive behavior or development is not fully understood. In this study, we examine how the nematode C. elegans integrates dietary information received by the gut with environmental signals to alter nervous system function. We have found that a signaling complex, called TORC2, acts in the gut to relay nutrition signals to alter hormonal signaling by the nervous system in C. elegans. Altered neuronal signaling in turn affects a food-dependent binary developmental decision in larvae, as well as food-dependent foraging behaviors in adults. Our results provide a mechanism by which animals prioritize specific signals such as feeding status to appropriately alter their development and/or behavior.

scholarly journals Neuroendocrine modulation sustains the C. elegans forward motor state

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Maria A Lim ◽  
Jyothsna Chitturi ◽  
Valeriya Laskova ◽  
Jun Meng ◽  
Daniel Findeis ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Transcriptome Profiling ◽  
Behavioral State ◽  
Forward Movement ◽  
C Elegans ◽  
Peptidergic Neuron ◽  
Homeobox Transcription Factor

Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

scholarly journals Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish

2021 ◽  
Author(s):  
Megan E Madden ◽  
Daumante Suminaite ◽  
Elelbin Ortiz ◽  
Jason J Early ◽  
Sigrid Koudelka ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Action Potential ◽  
Neural Circuit ◽  
Acoustic Stimuli ◽  
Larval Zebrafish ◽  
Axonal Conduction ◽  
Circuit Function ◽  
Cns Myelination ◽  
Conduction Properties

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, due to their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behaviour. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias towards reorientation behaviour instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.

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