The stress associated with starvation is accompanied by compensatory behaviours that enhance foraging efficiency and increase the probability of encountering food. However, the molecular details of how hunger triggers changes in the activity of neural circuits to elicit these adaptive behavioural outcomes remains to be resolved. We show here that AMP-activated protein kinase (AMPK) regulates neuronal activity to elicit appropriate behavioural outcomes in response to acute starvation, and this effect is mediated by the coordinated modulation of glutamatergic inputs. AMPK targets both the AMPA-type glutamate receptor GLR-1 and the metabotropic glutamate receptor MGL-1 in one of the primary circuits that governs behavioural response to food availability in C. elegans. Overall, our study suggests that AMPK acts as a molecular trigger in the specific starvation-sensitive neurons to modulate glutamatergic inputs and to elicit adaptive behavioural outputs in response to acute starvation.Animals often need to adapt to changes in food availability in order to survive. When food is in short supply and animals are starving, their energy reserves are low. To conserve energy, behaviours that are not essential to survival, like mating, are put on hold. Instead, animals channel their energies into foraging strategies that may help them find new food sources. These behavioural changes are likely to be caused by changes in brain activity triggered by starvation.It is not entirely clear how starvation changes the brain and consequently how an animal behaves. It is also difficult to study how the brain regulates behaviour in response to environmental changes like food availability in larger animals with more complex nervous systems. Instead, scientists often study less complex animals like a type of worm called C. elegans, because this model organism has a simpler nervous system and it is easier to observe its feeding behaviours. Previous observations have revealed that well-fed worms travel backwards when they are hungry, revisiting sites where they have previously found food. Yet, when the worms are starving, they move forward more frequently, presumably to find new sources of food.Now, Ahmadi and Roy show starving worms activate an enzyme called AMP-activated protein kinase (or AMPK for short). Worms genetically engineered to lack this enzyme tend to move backward when they are starved, instead of moving forward like typical starving worms. This shows that AMPK triggers a wider search for new food sources. Further experiments showed that AMPK acts to inhibit two receptors, which in turn, affects the activity of two different neurons. These two neurons work together to change the animal’s behaviour and boost the likelihood the animal will be able to find a new food source when food is scarce.More complex animals, including humans, also have the receptors and brain cells targeted by AMPK in response to starvation. Future studies are needed to determine whether a similar chain of events occurs in creatures with more complicated nervous systems.
Ahmadi, M., & Roy, R. (2016). AMPK acts as a molecular trigger to coordinate glutamatergic signals and adaptive behaviours during acute starvation. ELife, 5. https://doi.org/10.7554/elife.16349