Abstract
Sensory systems allow animals to detect, process, and respond to their environment. Food abundance is an environmental cue that has profound effects on animal physiology and behavior. Recently, we showed that modulation of longevity in the nematode Caenorhabditis elegans by food abundance is more complex than previously recognized. The responsiveness of the lifespan to changes in food level is determined by specific genes that act by controlling information processing within a neural circuit. Our framework combines genetic analysis, high-throughput quantitative imaging and information theory. Here, we describe how these techniques can be used to characterize any gene that has a physiological relevance to broad-range dietary restriction. Specifically, this workflow is designed to reveal how a gene of interest regulates lifespan under broad-range dietary restriction; then to establish how the expression of the gene varies with food level; and finally, to provide an unbiased quantification of the amount of information conveyed by gene expression about food abundance in the environment. When several genes are examined simultaneously under the context of a neural circuit, this workflow can uncover the coding strategy employed by the circuit.
Highlights
All organisms need to be able to sense and respond to changes to the environment to ensure their survival
By using the protocol outlined below, we identified a new class of genes involved in dietary restriction (DR) that bidirectionally modulate the lifespan response to food abundance and are involved in neural circuits that sense food[12] (Figure 1)
This method links two previously separate phenomena seen in C. elegans DR literature, bacterial deprivation and classical dietary restriction, allowing both dietary effects to be studied under one protocol
Summary
All organisms need to be able to sense and respond to changes to the environment to ensure their survival. The small physical size of the worm and its optical transparency lend themselves to in vivo imaging of both transcriptional and translational fluorescent reporters and utility of high-throughput technologies such as microfluidics[4] Together, these tools can be harnessed to examine how neural circuits direct animal behavior. The first can be termed 'classical DR', as it mirrors the changes seen in response to decreasing food levels in other organisms In this context, decreasing food abundance from ad libitum levels results in an increasing lifespan up until an optimum is reached, after this point longevity decreases with further reduction of food[6,7,9]. By applying the mathematical framework of information theory[14], we were able to quantify the amount of environmental information, in terms of bits, that is represented by the gene expression changes in daf-7 and tph-1 in specific neurons across different food levels. A certain level of programming proficiency is required to apply them in a meaningful way
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