scholarly journals Calcium dynamics regulating the timing of decision-making in C. elegans

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yuki Tanimoto ◽  
Akiko Yamazoe-Umemoto ◽  
Kosuke Fujita ◽  
Yuya Kawazoe ◽  
Yosuke Miyanishi ◽  
...  
Keyword(s):  
Decision Making ◽  
Calcium Channels ◽  
Molecular Mechanisms ◽  
Neuronal Responses ◽  
Odor Concentration ◽  
Nociceptive Neurons ◽  
C Elegans ◽  
Behavioral Decision ◽  
Voltage Gated Calcium Channels ◽  
Multiple Trials

Brains regulate behavioral responses with distinct timings. Here we investigate the cellular and molecular mechanisms underlying the timing of decision-making during olfactory navigation in Caenorhabditis elegans. We find that, based on subtle changes in odor concentrations, the animals appear to choose the appropriate migratory direction from multiple trials as a form of behavioral decision-making. Through optophysiological, mathematical and genetic analyses of neural activity under virtual odor gradients, we further find that odor concentration information is temporally integrated for a decision by a gradual increase in intracellular calcium concentration ([Ca2+]i), which occurs via L-type voltage-gated calcium channels in a pair of olfactory neurons. In contrast, for a reflex-like behavioral response, [Ca2+]i rapidly increases via multiple types of calcium channels in a pair of nociceptive neurons. Thus, the timing of neuronal responses is determined by cell type-dependent involvement of calcium channels, which may serve as a cellular basis for decision-making.

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 Developmental Control of CaV1.2 L-Type Calcium Channel Splicing by Fox Proteins

2009 ◽  
Vol 29 (17) ◽  
pp. 4757-4765 ◽  
Author(s):  
Zhen Zhi Tang ◽  
Sika Zheng ◽  
Julia Nikolic ◽  
Douglas L. Black
Keyword(s):  
Calcium Channels ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Membrane Excitability ◽  
Electrophysiological Properties ◽  
Culture Cells ◽  
Splicing Regulators ◽  
Voltage Gated Calcium Channels ◽  
Exon 9

ABSTRACT CaV1.2 voltage-gated calcium channels play critical roles in the control of membrane excitability, gene expression, and muscle contraction. These channels show diverse functional properties generated by alternative splicing at multiple sites within the CaV1.2 pre-mRNA. The molecular mechanisms controlling this splicing are not understood. We find that two exons in the CaV1.2 channel are controlled in part by members of the Fox family of splicing regulators. Exons 9* and 33 confer distinct electrophysiological properties on the channel and show opposite patterns of regulation during cortical development, with exon 9* progressively decreasing its inclusion in the CaV1.2 mRNA over time and exon 33 progressively increasing. Both exons contain Fox protein binding elements within their adjacent introns, and Fox protein expression is induced in cortical neurons in parallel with the changes in CaV1.2 splicing. We show that knocking down expression of Fox proteins in tissue culture cells has opposite effects on exons 9* and 33. The loss of Fox protein increases exon 9* splicing and decreases exon 33, as predicted by the positions of the Fox binding elements and by the pattern of splicing in development. Conversely, overexpression of Fox1 and Fox2 proteins represses exon 9* and enhances exon 33 splicing in the endogenous CaV1.2 mRNA. These effects of Fox proteins on exons 9* and 33 can be recapitulated in transfected minigene reporters. Both the repressive and the enhancing effects of Fox proteins are dependent on the Fox binding elements within and adjacent to the target exons, indicating that the Fox proteins are directly regulating both exons. These results demonstrate that the Fox protein family is playing a key role in tuning the properties of CaV1.2 calcium channels during neuronal development.

scholarly journals Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Martijn P. J. Dekkers ◽  
Felix Salfelder ◽  
Tom Sanders ◽  
Oluwatoroti Umuerri ◽  
Netta Cohen ◽  
...  
Keyword(s):  
Decision Making ◽  
Cognitive Processing ◽  
Sensory Neurons ◽  
Sensory Adaptation ◽  
Nociceptive Neurons ◽  
C Elegans ◽  
Motor Behaviors ◽  
Adaptation Mechanisms ◽  
Multiple Cell

AbstractA conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naïve animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animal’s behavioral state.

scholarly journals Histamine causes influx via T-type voltage-gated calcium channels in an enterochromaffin tumor cell line: potential therapeutic target in adverse food reactions

2019 ◽  
Vol 316 (2) ◽  
pp. G291-G303 ◽  
Author(s):  
Beatrix Pfanzagl ◽  
Victor F. Zevallos ◽  
Detlef Schuppan ◽  
Roswitha Pfragner ◽  
Erika Jensen-Jarolim
Keyword(s):  
Calcium Channels ◽  
Intracellular Calcium ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Trypsin Inhibitors ◽  
Enterochromaffin Cells ◽  
Neuroendocrine Cells ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Tnf Α

The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine (ACh), presumably via histamine 4 receptors, and weakly activated by histamine alone. Sensing these signals, enterochromaffin cells could participate in intestinal intolerance or allergic reactions to food constituents associated with elevated histamine levels. In this study we aimed to analyze the underlying molecular mechanisms. Inhibition by mepyramine and mibefradil indicated that histamine alone caused a rise in intracellular calcium concentration ([Ca2+]i) via histamine 1 receptors involving T-type voltage-gated calcium channels (VGCCs). Sensitivity to histamine was enhanced by pretreatment with the inflammatory cytokine tumor necrosis factor-α (TNF-α). In accordance with the relief it offers some inflammatory bowel disease patients, otilonium bromide, a gut-impermeable inhibitor of T-type (and L-type) VGCCs and muscarinic ACh receptors, efficiently inhibited the [Ca2+]i responses induced by histamine plus ACh or by histamine alone in P-STS cells. It will take clinical studies to show whether otilonium bromide has promise for the treatment of adverse food reactions. The cells did not react to the nutrient constituents glutamate, capsaicin, cinnamaldehyde, or amylase-trypsin inhibitors and the transient receptor potential channel vanilloid 4 agonist GSK-1016790A. The bacterial product butyrate evoked a rise in [Ca2+]i only when added together with ACh. Lipopolysaccharide had no effect on [Ca2+]i despite the presence of Toll-like receptor 4 protein. Our results indicate that inflammatory conditions with elevated levels of TNF-α might enhance histamine-induced serotonin release from intestinal neuroendocrine cells. NEW & NOTEWORTHY We show that histamine synergistically enhances the intracellular calcium response to the physiological agonist acetylcholine in human ileal enterochromaffin tumor cells. This synergistic activation and cell activation by histamine alone largely depend on T-type voltage-gated calcium channels and are inhibited by the antispasmodic otilonium bromide. The cells showed no response to wheat amylase-trypsin inhibitors, suggesting that enterochromaffin cells are not directly involved in nongluten wheat sensitivity.

scholarly journals Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation

2021 ◽  
Author(s):  
Martijn P.J. Dekkers ◽  
Felix Salfelder ◽  
Tom Sanders ◽  
Oluwatoroti Umuerri ◽  
Netta Cohen ◽  
...  
Keyword(s):  
Decision Making ◽  
Cognitive Processing ◽  
Sensory Neurons ◽  
Sensory Adaptation ◽  
Nociceptive Neurons ◽  
C Elegans ◽  
Motor Behaviors ◽  
Adaptation Mechanisms ◽  
Multiple Cell

A conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naive animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animal′s behavioral state.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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