Metaplasticity in the ventral pallidum as a potential marker for the development of diet-induced obesity

A major driver of obesity is the increasing palatability of processed foods. Although reward circuits promote the consumption of palatable food their involvement in obesity remains unclear. The ventral pallidum (VP) is a key hub in the reward system that encodes the hedonic aspects of palatable food consumption and participates in various proposed feeding circuits. However, there is still no evidence for its involvement in developing diet-induced obesity. Here we examine, using male C57bl6/J mice and patch-clamp electrophysiology, how chronic high-fat-high-sugar (HFHS) diet changes the physiology of the VP and whether mice that gain the most weight differ in their VP physiology from others. We found that 10-12 weeks of HFHS diet decreased the excitability of VP neurons, but without major change in synaptic inhibitory input. Within the HFHS group, obesity-prone (OP, top 33% weight gainers) mice had a less excitable VP compared to obesity-resistant (OR, bottom 33% weight gainers) mice and showed short- and long-term potentiation of incoming inhibitory inputs. Moreover, we found that long-term potentiation of the inhibitory inputs to the VP may exist in OP mice before exposure to HFHS and may thus serve as a marker for the predisposition to become obese. These data point to the VP as a critical player in obesity and suggest that hypoactivity in the VP may play a significant role in promoting overeating of palatable food.