Developing a Quantitative Description of Feeding Behavior and Its Response to Perturbations

Abstract

The regulation of food intake plays a major role in controlling energy availability in organisms. Feeding regulation needs to be robust to common perturbations, to ensure continued thriving of the organism. Here, I present the behavioral response of an animal to challenging feeding conditions: We assay low and temporally-varying levels of food, as well as feeding after stressful sleep-deprivation. I test the effect of these conditions in the nematode Caenorhabditis elegans, which is a model organism that shares conserved regulatory mechanisms with insects and vertebrates. ,First, I describe a scalable automated method for measuring the food intake of \textit{C. elegans} in controlled environments. This approach enables unbiased measurements for prolonged periods, high throughput, and the possibility of controlled, dynamically changing feeding environments. The automated analysis compares well with scoring pumping by visual inspection, a common practice in the field. ,I then apply our automated method to investigate the regulation of feeding in response to variable food levels. Animals need to regulate their food intake in response to the availability of food in the environment. Frequently, animals have to integrate information from the environment to decide whether to expend energy feeding, or wait until conditions improve. I find that animals upregulate their feeding rate by changing the time spent in bursts of rapid pumping relative to pauses. We expose the animals to a dynamically changing environment with pulses of high and no food. We find that animals respond stochastically, only upregulating their pumping rate in response to some of the high food pulses, with no apparent pattern. This behavior cannot be explained by traditional models of feeding.,Using our newly developed tracking method, we investigate the effect of sleep deprivation on the highly active tissue of the pharynx. We show that during the last developmental stage of the organism, animals are vulnerable to damage through sleep deprivation. We find that adult animals exhibit deficits in feeding 12 hours after deprivation. Moreover, feeding defects were exacerbated when a transcription factor active during stressful periods and effective in mitigating downstream damage was inactive. We show that these downstream effects include the mitochondrial unfolded protein response and endoplasmatic reticulum stress. These observations link cellular damage directly to sleep deprivation, indicating that a protective mechanism exists to shield adult feeding behavior from damage.,Finally, I show that an information-theoretic model can recapitulate key features of the animals' feeding behavior. We find that the temporal pattern of feeding behavior is shaped by a balance between the need to obtain information about a changing environment and the exploitation of the available food. The model shows how a feeding pattern consisting of bursts and pauses can be advantageous for an animal. The model also accounts for stochastic responses to oscillating food levels, which was observed experimentally. ,Taken together, these results show how a quantitative description of behavior can be used to understand strategies that animals employ to ensure survival in challenging conditions.