Behavioural phenotyping of GFRAL neurons in mood and motivation

The neural pathways that mediate appetite control many other functions, including mood, motivation, memory, attention and arousal, suppression of competing drives such as mating or fear, and stress attenuation. Information about current metabolic status arrives at the brain in the form of a complex milieu of circulating hormonal and nutrient factors that the brain then turns into a ‘hunger’ or ‘satiety’ signal. Some hormonal factors of metabolic state, such as leptin and ghrelin also influence mood-related behaviours in mice. One novel candidate for regulating both mood and appetite is growth and differentiation factor 15 (GDF15). The receptor for GDF15, GFRAL, was recently discovered and it is expressed solely in the brainstem. GFRAL activation by GDF15 results in neuronal in brain areas shown to be important in mood-related behaviour, aversion, and avoidance as well as appetite suppression. This suggests that the neural circuits activated by GDF15-GFRAL signalling regulate both mood and appetite processing. This leads to a key unanswered question: does GDF15-GFRAL signalling concurrently affect mood and appetite regulation? This project will use advanced genetic techniques and mouse behaviour testing to answer this question.