A Circuit Neuroscience Seminar (CNS)

Obesity, one of the leading causes of preventable death in the world, is characterized by an inability to resist hunger, which leads to overeating and obesity along with associated detrimental health disorders. A healthy animal adapts competing motivations to engage with food, water, or conspecifics according to current physiological needs as well as opportunities.

Yet, the neuronal mechanisms of sensing and ranking nutritional needs remain poorly understood. Furthermore, it is unknown how animals integrate social drive with feeding or drinking drives to resolve the conflict between hunger, thirst and social needs.

We combined single-cell calcium imaging in freely behaving mice, optogenetics, and chemogenetics, we show that two distinct neuronal populations of the lateral hypothalamus (LH) guide increasingly hungry animals through behavioral choices between nutritional and social rewards. Despite hunger or thirst, leptin receptor-expressing (LepRLH) neurons limit feeding or drinking while promoting social interaction. Accordingly, increased food consumption is marked by increasing inhibition of a leptin-sensitive LepRLH subpopulation at a fast time scale. Conversely, neurotensin-expressing LH neurons specifically prioritize drinking despite hunger pressure and relegate social needs. Thus, hunger and thirst gate both LH populations in a complementary manner to enable the fulfillment of multiple essential needs.

In this study, we demonstrate how deep brain structures allow an animal to integrate the need for food, water, and social interaction and to resolve the conflict between hunger, thirst, and social drive in an adaptive and flexible manner. Importantly, we establish a basis to understand how experiences of scarcity affect the potentially maladaptive ranking of conflicting motivations, which may facilitate, for example, over-eating and the development of obesity.

Join via Zoom: https://bristol-ac-uk.zoom.us/j/94996372891