Agouti-related peptide (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. Thus, Agrp neurons respond to environmental stimuli that convey information relevant to food seeking and food detection. However, when foraging, food is not the only potential environmental stimulus to be encountered; other such stimuli include stressors signalling threat, fear or danger. This study aimed to investigate the effects of stressors on Agrp neural activity and whether optogenetic control of Agrp neurons can simulate the stressful event.
To do this, we combined fibre photometry with various stress paradigms. We recorded Agrp neuronal responses using GCaMP7s in fed and fasted mice during restraint stress, novel environment/object exposure and elevated zero maze. In both, fed and fasted mice, Agrp activity dropped when exposed to stress but less compared to food.
Our experiments show that Agrp neurons are transiently inhibited by acute stressors but rebound immediately once the stressful event has passed. With this insight, we demonstrated that mice learn to avoid the Y-maze arm paired with optogenetically suppressed Agrp activity.
Together our results suggest that a transient decrease in Agrp neural activity encodes a broader “stop foraging” signal that has differential outcomes for food consumption based on the presence of stressful stimuli. Current studies using axonal GGamp aim to reveal the inhibitory inputs and the identity and pathway of stress responsive Agrp neurons.