C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves

Witham, Emily A.; Comunian, Claudio; Ratanpal, Harkaranveer; Skora, Susanne; Zimmer, Manuel; Srinivasan, Supriya

doi:10.1016/j.celrep.2016.01.052

Cited by 40 publications

(73 citation statements)

References 48 publications

(65 reference statements)

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“…This would be a potential means of anticipating starvation that would enable animals to rapidly relocate to more optimal environments. Given that C. elegans lose approximately 70% of their body fat within 2-3 h of fasting (40), the rapid reversal of exploratory behavior is an important survival mechanism in these animals.…”

Section: Discussionmentioning

confidence: 99%

“…To more directly investigate whether increased fat storage in ets-5 mutant animals causes reduced exploration, we decreased body fat levels in the intestine by RNAi of pod-2 (encoding an acetyl-CoA carboxylase that produces malonyl CoA, a crucial precursor of fatty acid synthesis) and elo-2 (encoding a palmitic acid elongase that converts C16:0 fatty acids to C18:0 fatty acids) (39)(40)(41). We found that pod-2 and elo-2 RNAi partially suppressed In addition, the exploratory defect of ets-5(tm1734) mutant animals is fully suppressed when animals are grown on this inedible food source.…”

Section: Malnutrition Suppresses Exploration Defects Caused By Loss Omentioning

confidence: 99%

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The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Juozaityte

Pladevall‐Morera

Podolska

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Animal behavior is shaped through interplay among genes, the environment, and previous experience. As in mammals, satiety signals induce quiescence in Caenorhabditis elegans. Here we report that the C. elegans transcription factor ETS-5, an ortholog of mammalian FEV/Pet1, controls satiety-induced quiescence. Nutritional status has a major influence on C. elegans behavior. When foraging, food availability controls behavioral state switching between active (roaming) and sedentary (dwelling) states; however, when provided with high-quality food, C. elegans become sated and enter quiescence. We show that ETS-5 acts to promote roaming and inhibit quiescence by setting the internal "satiety quotient" through fat regulation. Acting from the ASG and BAG sensory neurons, we show that ETS-5 functions in a complex network with serotonergic and neuropeptide signaling pathways to control food-regulated behavioral state switching. Taken together, our results identify a neuronal mechanism for controlling intestinal fat stores and organismal behavioral states in C. elegans, and establish a paradigm for the elucidation of obesity-relevant mechanisms.ETS transcription factor | neuronal signaling | satiety | fat levels | quiescence A nimal behavior is strongly influenced by the availability of food. In invertebrates and vertebrates, appetite, locomotor activity, and sleep rhythms are all driven by nutritional state (1-7). When malnourished, animals seek out a new food source by actively exploring their environment (roaming), whereas animals that are well fed tend to explore less (dwelling) and when fully sated enter a quiescent or sleep-like state (1-3, 8, 9). Transitions between these behavioral states can be regulated by sensory perception of external stimuli and through gut signals or other internal cues that are generated according to food quality (3,4,6).Initial evidence for neuronal regulation of feeding behavior was shown in mammals using hypothalamic lesions (10). Sectioning of specific regions within the rat hypothalamus evoked opposing behaviors. Removal of one section caused overeating and obesity, whereas removal of an adjacent section resulted in starvation owing to reduced eating (10). Subsequent studies showed that the pro-opiomelanocortin-expressing neurons in the hypothalamus function to suppress feeding, whereas a hypothalamic region that contains neuropeptide Y/agouti-related protein-expressing neurons promotes feeding (11). These adjacent brain regions integrate signals received from the gut that report satiety (12). The nutritive content of food itself also serves as a potent regulator of behavior. In mammals, a diet loaded with fats and sugars stimulates overfeeding and leads to obesity (13). In addition, rats can learn to select a source of food based exclusively on its nutritional value in the absence of external cues (14).In Caenorhabditis elegans, as in mammals, nutritive value is a behavioral stimulus (1, 4). Nematodes exhibit different behaviors when cultured on low-quality food compared to high-quality...

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Section: Discussionmentioning

confidence: 99%

Section: Malnutrition Suppresses Exploration Defects Caused By Loss Omentioning

confidence: 99%

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Juozaityte

Pladevall‐Morera

Podolska

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Given their unique anatomic position, these neurons are hypothesized to mediate bidirectional communication between nervous system and peripheral tissues as they have the capacity to both release and detect circulating signals. Interestingly, neural serotonin signaling is thought to promote intestinal fat metabolism through the release of an neuroendocrine signal from URX neurons [31,32] and fluctuations in peripheral fat metabolism modulate the tonic activity of URX [102]. We find that targeted expression of egl-2(gf) in only the body cavity neurons is sufficient to block the feeding increasing effects of serotonin and mimic the effects of loss of acox-1 ( Figure 7B).…”

Section: Acox-1 Regulates Urx Body Cavity Neuron Activity To Limit Fementioning

confidence: 86%

“…To directly assess the effects of ACOX-1 activity on body cavity neuron function, we measured intracellular Ca 2+ transients from the URX body cavity neurons using the genetically-encoded calcium reporter GCaMP5K [102,104]. We selected URX neurons as calcium dynamics from these cells have been well documented and intriguingly their activity has recently been shown to be modulated by internal metabolic cues and starvation [102,[105][106][107]. URX neurons play a well-documented role in oxygen sensing and are robustly and rapidly activated under atmospheric conditions (21% oxygen) ( Figure 8A and 8C) [105,[108][109][110].…”

Section: Acox-1 Regulates Urx Body Cavity Neuron Activity To Limit Fementioning

confidence: 99%

Intestinal peroxisomal fatty acid β-oxidation regulates neural serotonin signaling through a feedback mechanism

Bouagnon

Srivastava

Panda

et al. 2019

Preprint

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The ability to coordinate behavioral responses with metabolic status is fundamental to the maintenance of energy homeostasis. In numerous species including C. elegans and mammals, neural serotonin signaling regulates a range of food-related behaviors. However, the mechanisms that integrate metabolic information with serotonergic circuits are poorly characterized. Here, we identify metabolic, molecular, and cellular components of a circuit that links peripheral metabolic state to serotonin-regulated behaviors in C. elegans. We find that blocking the entry of fatty acyl-CoAs into peroxisomal β-oxidation in the intestine results in blunting of the effects of neural serotonin signaling on feeding and egg-laying behaviors. Comparative genomics and metabolomics revealed that interfering with intestinal peroxisomal β-oxidation results in a modest global transcriptional change but significant changes to the metabolome, including a large number of changes in ascaroside and phospholipid species, some of which affect feeding behavior. We also identify body cavity neurons and an ether-ago-go related (EAG) potassium channel that functions in these neurons as key cellular components of the circuitry linking peripheral metabolic signals to regulation of neural serotonin signaling. These data raise the possibility that the effects of serotonin on satiety may have their origins in feedback, homeostatic metabolic responses from the periphery.

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“…Our script used animal centroid coordinate data to determine mean population headings (imported from Image-Pro Plus, see above). Worm responses to diverse stimuli change over time based on their internal state (Gosh et al, 2016;Witham et al, 2016;Klein et al, 2017). To compare animals in similar states, we binned each animal track into 5% intervals for each trajectory in order to normalize headings for animals that completed the same proportion of their total trajectory.…”

Section: Animal Directional Headingsmentioning

confidence: 99%

Unbiased analysis of C. elegans behavior reveals the use of distinct turning strategies during magnetic Orientation

Bainbridge

McDonald

Ahlert

et al. 2019

Preprint

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To successfully navigate their surroundings, animals detect and orient to environmental stimuli possessing unique physical properties. Most animals can derive directional information from spatial or temporal changes in stimulus intensity (e.g. chemo- and thermo-taxis). However, some biologically relevant stimuli have constant intensity at most organismal scales. The gravitational and magnetic fields of the earth are examples of uniform stimuli that remain constant at most relevant scales. While devoid of information associated with intensity changes, the vectorial nature of these fields intrinsically encodes directional information. While much is known about behavioral strategies that exploit changes in stimulus intensity (gradients), less is understood about orientation to uniform stimuli. Nowhere is this truer than with magnetic orientation. While many organisms are known to orient to the magnetic field of the earth, how these animals extract information from the earth’s magnetic field remains unresolved.Here we use the nematode C. elegans to investigate behavioral strategies for orientation to magnetic fields, and compare our findings to the better characterized chemical and thermal orientation strategies. We used an unbiased cluster analysis to categorize, quantify, and compare behavioral components underlying different orientation strategies as a way to quantify and compare animal orientation to distinct stimuli. We find that in the presence of an earth-like magnetic field, worms perform acute angle turns (140-171°) that significantly improved their alignment with the direction of an imposed magnetic vector. In contrast, animals performed high amplitude turns (46-82°) that significantly increased alignment of their trajectory with the preferred migratory angle. We conclude that C. elegans orients to earth-strength magnetic fields using two independent behavioral strategies, in contrast to orientation strategies to graded stimuli. Understanding how C. elegans detects and orients to magnetic fields will provide useful insight into how many species across taxa accomplish this fascinating sensory feat.

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C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves

Cited by 40 publications

References 48 publications

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

The ETS-5 transcription factor regulates activity states in Caenorhabditis elegans by controlling satiety

Intestinal peroxisomal fatty acid β-oxidation regulates neural serotonin signaling through a feedback mechanism

Unbiased analysis of C. elegans behavior reveals the use of distinct turning strategies during magnetic Orientation

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