Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

The Role of Hunger Sensing and Signalling in Motivation, Extinction and Reversal Learning. (#106)

Jiachen Hu 1 , Wang Lok So 1 , Lotus Jeffs 1 , Vasili Drakopoulos 1 , Jiaxin Huang 1 , Romana Stark 1 , Alex Reichenbach 1 , Zane Andrews 1
  1. Monash University, Clayton, VIC, Australia

AgRP neurons, known for their role in hunger sensing, are crucial for maintaining energy homeostasis. In response to negative energy balance, these neurons become active to promote food consumption and food-seeking behaviours, including motivation, learning, memory, and anxiety. One way in which AgRP neurons sense hunger is when ghrelin, commonly known as the hunger hormone, binds to the ghrelin receptor (Growth Hormone Secretagogue Receptor; GHSR). While AgRP neurons are located exclusively in the hypothalamus, GHSR-expressing neurons are found in various brain regions, including the brain stem, hippocampus, and ventral tegmental area (VTA). Additionally, a small population of GHSR neurons in the arcuate nucleus (ARC) do not express AgRP. While it is well known that artificially stimulating ARCAgRP neurons increases food consumption by enhancing motivation, the role of ARCGHSR+ neurons in this process remains unclear. This study investigates the roles of ARCGHSR+ or ARCGHSR+/AgRP- neurons in motivation and both extinction and reversal learning. We used GHSR cre and AGRP flp mice to optogenetically control either all ARCGHSR+ or ARCGHSR+/AgRP- neurons. This technique allowed us to closely examine the relationship between neuronal activity and animal behaviour. We assessed motivation, extinction and reversal learning using the home-cage feeding experimental device (FED3), which tracks mice's learning patterns over time. Photostimulation of GHSR neurons enhanced motivation, task engagement, exploration. However, it also led to more stereotyped food-seeking behaviours and reduced extinction and reversal learning. Conversely, photostimulation of ARCGHSR+/AgRP- neurons did not significantly impact motivation, extinction and reversal learning. These results suggest that ARCGHSR+/AgRP- neurons may have a different role in the ARC, potentially in regulating pituitary hormone release.