The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans

Abstract

The mammalian endocannabinoid system, comprised of the endocannabinoids AEA (N-arachidonoyl-ethanolamine) and 2-AG (2-Arachidonoylglycerol), their receptors, CB1 and CB2, and their metabolic enzymes, is believed to integrate internal energy state and external food cues to modulate feeding. For example, cannabinoids can increase preference for more palatable, calorically dense food: a response called hedonic amplification, colloquially known as "the munchies." In mammals, cannabinoids can increase sensitivity to odors and sweet tastes, which may underlie amplification. We use C. elegans, an omnivorous bacterivore, as a model in which to investigate the neurophysiology of hedonic amplification. We found that exposure to AEA increases the worms' preference for strongly preferred (more palatable) bacteria over weakly preferred (less palatable) bacteria, mimicking hedonic amplification in mammals. Furthermore, AEA acts bidirectionally, increasing consumption of strongly preferred bacteria while decreasing consumption of weakly preferred bacteria. We also found that deletion of the putative CB1 homolog, npr-19, eliminates hedonic amplification, which can be rescued by expression of wild type npr-19 or human CB1, establishing a humanized worm for cannabinoid signaling studies. Deletion of the olfactory neuron AWC, which directs chemotaxis to food, abolishes hedonic amplification. Consistent with this finding, calcium imaging revealed that AEA bidirectionally modulates AWC activity, increasing its responses to strongly preferred food and decreasing its response for weakly preferred food. In a GFP expression analysis, we found that npr-19 is expressed in approximately 21 neuron classes but, surprisingly, not in AWC. Although AEA's effect could be mediated by NPR-19-expressing neurons presynaptic to AWC, nearly complete elimination of fast synaptic transmission, via the mutation unc-13(e51), had no effect on modulation. Instead, it appears that AEA modulates AWC by activating one or more npr-19-expressing neurons that release a diffusible neuromodulator to which AWC is sensitive.

Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo verbana

“…The endocannabinoid system lends itself to comparative study since endocannabinoid transmitters, 2-AG and AEA, are found across vertebrate and invertebrate species [6,11,12]. Similar to vertebrates, endocannabinoid signaling in invertebrates has been shown to contribute learning and memory, and nociception, feeding, axon growth and development, and sensory processing [12][13][14][15][16][17][18]. Less detail in known about the molecular signaling mechanisms of endocannabinoids within invertebrates.…”