Diverse states and stimuli tune olfactory receptor expression levels to modulate food-seeking behavior

Abstract

Animals must weigh competing needs and states to generate adaptive behavioral responses to the environment. Sensorimotor circuits are thus tasked with integrating diverse external and internal cues relevant to these needs to generate context-appropriate behaviors. However, the mechanisms that underlie this integration are largely unknown. Here, we show that a wide range of states and stimuli converge upon a single Caenorhabditis elegans olfactory neuron to modulate food-seeking behavior. Using an unbiased ribotagging approach, we find that the expression of olfactory receptor genes in the AWA olfactory neuron is influenced by a wide array of states and stimuli, including feeding state, physiological stress, and recent sensory cues. We identify odorants that activate these state-dependent olfactory receptors and show that altered expression of these receptors influences food-seeking and foraging. Further, we dissect the molecular and neural circuit pathways through which external sensory information and internal nutritional state are integrated by AWA. This reveals a modular organization in which sensory and state-related signals arising from different cell types in the body converge on AWA and independently control chemoreceptor expression. The synthesis of these signals by AWA allows animals to generate sensorimotor responses that reflect the animal’s overall state. Our findings suggest a general model in which sensory- and state-dependent transcriptional changes at the sensory periphery modulate animals’ sensorimotor responses to meet their ongoing needs and states.

Dissecting the Functional Organization of theC. elegansSerotonergic System at Whole-Brain Scale

“…S5B). Consistent with this, our previous ribotagging data in well-fed versus fasted animals showed no change in expression of the six receptors (McLachlan et al, 2022; though we cannot rule out more subtle changes in the levels of expression in subsets of cells). Each receptor was expressed in at least 8 of the 118 C. elegans neuron classes, with a range of 8-24 neuron classes per receptor (Fig.…”

“…5 below). In addition, the overall levels of mRNA translation for each of the six receptors in well-fed versus fasted animals were not significantly different (based on our previous ribotagging results in McLachlan et al, 2022, which used animals of the same age and the same fasting duration). This suggests that the impact of MOD-1 and LGC-50 receptor activation on neural circuit activity may be enhanced by fasting.…”

“…This resulted in some individual neuron classes expressing as many as five different serotonin receptor genes. Importantly, we used an identical strategy to construct T2A-mNeonGreen reporters for several other GPCRs (in the olfactory receptor gene family) that showed completely different expression patterns, indicating that correlated expression among the serotonin receptors is not an artifact of the reporter strategy (McLachlan et al, 2022). This high incidence of co-expression of the serotonin receptors could plausibly underlie some of the functional interactions among the receptors.…”

Evolutionary transitions from female to hermaphrodite reproduction remodel olfactory and mating-receptive behaviors

“…18 AWA receptor gene expression is further modified by food deprivation. 48,50 The model that AWA receptor expression contributes to the transition from female to hermaphrodite behaviors makes testable hypotheses for future studies of sex-specific receptor expression in C. nigoni and C. briggsae .…”

Pheromone-based animal communication influences the production of somatic extracellular vesicles

“…More than 1,300 G protein-coupled receptors (GPCRs) mediate this communication in C. elegans 30 . Internal states and environmental conditions can modulate GPCRs expression to affect worm behavior [31][32][33][34] . To identify the receptor(s) responsible for ascaroside-mediated alterations in exopher formation, we performed RNA-sequencing of animals grown either as a single animal or in a 10-hermaphrodites population (Supplementary Fig.…”