Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680788
Title: Delineation of a gut brain axis that regulates context-dependent feeding behaviour of the nematode Caenorhabditis elegans
Author: Dalliere, Nicolas
ISNI:       0000 0004 5917 1090
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2016
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Abstract:
Food directed behaviours execute key aspects of an animal’s ability to maintain a balanced energy intake. This homeostasis needs to integrate external cues that define the source and suitability of food and metabolic states that define requirements for food. In a human context, impairments in the mechanisms underlying feeding behaviours may result in maladapted responses that eventually lead to obesity and other metabolic diseases (e.g. bulimia and anorexia nervosa). Given the fundamental nature of this animal behaviour, simple invertebrate models can provide a route to facilitate understanding in higher animals and humans. In this study, the adaptive behavioural response of the nematode C. elegans to food is used to investigate the fundamental mechanisms underlying feeding behaviour. This utilized the behavioural transition of the worm’s feeding organ, the pharynx, during presentation and removal of food. Feeding behaviour was assayed in intact worms by counting the contraction-relaxation cycles of the pharynx. On food this shows a high pumping rate of around 250 pump.min-1 (ppm). In contrast, when transferred onto a no food arena, the pumping rate is reduced to almost zero. Subsequently, in the absence of food, the worms display a two phase adaptive pumping behaviour. The first ‘early phase’ has a slow increase of pumping rate up to ~30-40 ppm followed by a ‘late phase’ where the pumping rate becomes highly variable, fluctuating from very low (0-10 ppm) to high (100-150 ppm) values, and lasts at least up to 8 hours following the initial removal of food. Using this paradigm, I demonstrated that pumping behaviours were more than a simple ON/OFF switch but instead actively modulated by distinct neuronal circuits depending on the food context. Both non-peptidergic transmitters and neuropeptides are involved in the control of this adaptive response in a complex manner with the manner of regulation depending on the food context. For example, glutamate signalling stimulates pumping ‘on’ food while acting to reduce pumping in its absence. On food, the neurons M3 are known to increase the pumping rate via the release of glutamate. In this thesis, I have shown that a significant part of the glutamate associated with glutamatergic inhibitory tone in response to food removal is released from the pharyngeal neurons I2 and acts through the AVR-14 glutamate-gated chloride channel. In pharyngeal and central nervous system, shows no aberrant pumping behaviours, suggesting an important role for the worm’s enteric system. Genetic and environmental manipulation of sensory structures was used to address the modalities mediating the pumping behaviours. This analysis revealed that specific sensory structures and pathways are utilized in the distinct ‘on’ and ‘off’ food context. Strikingly, perception of odours from food by chemosensory neurons of the central nervous system does not contribute to the pumping rate as mutants in which the sensory functions of these neurons are deficient show no aberrant pumping behaviour in the presence of food. Rather mechanical cues seem important. The same chemosensory mutants show pumping rates off food that indicate they do not perceive food removal. This contrasts with the observation highlighted by RIP ablation and indicates that extrapharyngeal structures are involved but must be utilizing volume transmission. Investigation of the role of neurohormonal signalling was assessed by analysis of neuropeptide deficient and synaptic protein mutants. In egl-3 the pumping rate is totally abolished during food-deprivation. In contrast, unc-31 showed an elevated pumping rate ‘off’ food. These results suggest that neuropeptide signalling is required both to maintain the low level of pumping and to reduce it in the absence of food. Investigation of the role of individual neuropeptides supports the above. Interestingly both pharyngeally and extrapharyngeally expressed peptides support these phenotypes, consistent with a model in which food signals, involving discrete enteric and central nervous system, regulate the worm’s feeding behaviours. Overall, this thesis provides new insight into the neural substrates of behavioural plasticity in C. elegans. It shows that even a simple nematode with a nervous system of 302 neurons can show complex regulation of feeding behaviours, involving multiple pathways, which conceptually resonates with higher organisms’ organisation.
Supervisor: Holden-Dye, Linda ; O'connor, Vincent Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.680788  DOI: Not available
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