Kono, Karina et al. (2019) International Worm Meeting "Inter-tissue signals drives inter-animal communication driving collective food-seeking behavior in C. elegans."

Lau, Hiu, Liu, Zheng, Tames, Maria, Kono, Karina, Rodrigues, Pedro, Yang, Claire, Chalasani, Sreekanth, Sharpee, Tatyana, Dubova, Ilir, Cecere, Zachary, Schroeder, Frank

[International Worm Meeting, 2019]

Neural circuits extract relevant sensory information from their environment and integrate internal state information and prior experience to generate robust behaviors. However, less is known how internal state information, including hunger affects neural circuit function and behavioral readouts. We combined food-deprivation with sensory integration assay where animals cross a repellent barrier to reach an attractant source. We found that food-deprived animals are more likely to cross the repellent barrier compared to controls. Specifically, we find that food-deprivation affects repellent sensitivity and is reversible. Next, we mapped the molecular pathway sensing and integrating this internal state. We show that MML-1 (a glucose-responsive bHLH/leucine zipper Mondo A homolog) detects the lack of glucose in the intestine and releases an AEX-5 convertase processed peptides using dense core vesicles. These peptides are sensed by DAF-2 insulin receptors on ASI neurons using a non-canonical mTOR complex. Downstream of this intestine-ASI signal, food-deprived animals alter the ascarosides that they secrete affecting the rest of the population. These studies show how intestinal signals modify neuronal signaling and alter inter-animal communication modifying collective behavior.

Matty, Molly et al. (2021) International Worm Meeting "Food Deprivation Induces Behavioral Changes that Require Metabolic Reprogramming and Non-Canonical Insulin Signaling"

Chalasani, Sreekanth, Singh, Anupama, Matty, Molly, Kono, Karina, Lau , Hiu

[International Worm Meeting, 2021]

Behavioral changes are easily attributable to external influences such as temperature, light exposure, and chemical stimuli. However, the effects of internal states such as infection status, stress, and hunger on animal behavior are often less obvious. We sought to determine how an internal state modifies animal behavior and define the pathways necessary to encode the behavioral change. Sensory integration is a conserved behavior in which an animal, or population of animals, must integrate attractive and repulsive signals simultaneously to decide whether to approach or avoid a cue. We conducted sensory integration assays in which populations of C. elegans are presented with an attractant, diacetyl, just beyond a repellant copper barrier. We show that acute food deprivation reversibly reduces copper sensitivity, allowing animals to engage in a "risky behavior": starved animals cross the toxic copper barrier to reach the attractant ~4 times more often than well-fed animals. Our results suggest that decreased copper sensitivity in food-deprived animals requires the transcription factors MondoA and HLH-30 within intestinal cells, which likely detect and respond to the lack of food. Others have shown HLH-30 translocation to intestinal nuclei is correlated with the expression of a few insulin-like peptides, many of which we show are required for the hunger-induced behavioral change. The insulin receptor DAF-2 is required to sense and respond to these insulin-like peptides. We demonstrate that expression of daf-2 and downstream non-canonical insulin signaling molecules in the ASI chemosensory neurons sufficiently rescues this food deprivation-induced risk-taking behavior. Our work suggests that the internal state of hunger or food sensation links animal behavior to intestinal metabolism and neuronal function.