Hunger is a complex physiological drive that affects both the mood and motivation of an organism to promote food consumption and restore energy balance. Agrp neurons in the hypothalamus sense hunger and promote feeding, however when food is unavailable, Agrp neurons promote adaptive behaviours by reducing anxiety and increasing food-seeking behaviour. Thus Agrp neurons respond to environmental stimuli that convey information relevant to food seeking and food detection. However, when foraging within an environment, food is not the only potential environmental stimulus to be encountered; other such stimuli include acute stressors signalling danger. Although fasting and hunger has been shown to influence stress reactivity and endocrine signals, such as corticosterone; whether acute stressors regulate Agrp neural activity remains unknown. The aim of this study was to investigate the effects of acute stressors on Agrp neural activity in fed and fasted mice.
We recorded Agrp neuronal responses using GCaMP7s in fed and fasted mice during various stressors. Agrp activity dropped during restraint stress significantly but returned to baseline upon release. Similarly, Agrp neural activity decreased as animals entered a novel environment or approached a novel object. In the elevated zero maze, Agrp neuronal activity in fed and fasted mice decreased transiently when transitioning into the open part of the zero maze.
Our experiments show that Agrp neurons are transiently inhibited by acute stressors but rebound immediately once the stressful event has passed. The suppression of Agrp activity is similar to that seen in response to food detection therefore we suggest that a transient decrease in Agrp neural activity encodes a broader “stop foraging” signal. In the case of food detection a “stop foraging” signal facilitates consumption, however in response to a stressful stimulus, this “stop foraging” shifts attention to other adaptive behaviours to acutely prioritise safety over foraging.