Metaplasticity in the Ventral Pallidum as a Potential Marker for the Propensity to Gain Weight in Chronic High-Calorie Diet

Abstract

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 hyperpolarized and decreased the firing rate of VP neurons without a major change in synaptic inhibitory input. Within the HFHS group, the top 33% weight gainers (WGs) had a more hyperpolarized VP with longer latency to fire action potentials on depolarization compared with bottom 33% of weight gainers (i.e., non-weight gainers). WGs also showed synaptic potentiation of inhibitory inputs both at the millisecond and minute ranges. Moreover, we found that the tendency to potentiate the inhibitory inputs to the VP might exist in overeating mice even before exposure to HFHS, thus making it a potential property of being an overeater. These data point to the VP as a critical player in obesity and suggest that hyperpolarized membrane potential of, and potentiated inhibitory inputs to, VP neurons may play a significant role in promoting the overeating of palatable food.

Single-cell sequencing of rodent ventral pallidum reveals diverse neuronal subtypes with non-canonical interregional continuity

“…Building upon evidence that VP is altered by exposure to high-fat diet ( 26; 27 ), controls preference for fatty foods ( 48 ), and modulates weight gain from high-fat diet ( 49 ), we investigated how prolonged high-fat diet changes widespread gene expression in VP. We detected DEGs in all cell types when comparing gene expression after 5 w of high-fat diet to 5 w of matched diet and to 2 w of standard diet.…”

“…Within VP, there was remarkable homology between mouse and rat tissue, both in subclass representation and marker gene expression, including developmental transcription factors and extracellular signaling proteins. Guided by the general role of VP in feeding ( 21–23 ) and specific alterations to VP following high-fat diet consumption ( 26; 27 ), we assessed the impact of prolonged exposure to high fat diet on VP transcription, and we found changes in the expression of genes related to oxidative phosphorylation and inhibitory signaling mechanisms. Our results demonstrate considerable transcriptional heterogeneity in VP as well as a gradient of subclass representation across space, eschewing anatomical boundaries, lending new insight into the regional identity of VP and its incomplete separation from adjacent (including non-basal ganglia) areas.…”

Multimodal interrogation of ventral pallidum projections reveals projection-specific signatures and opposite roles in cocaine withdrawal

“…Slice preparation -As described before [14][15][16] . Mice were anesthetized with 150 mg/kg Ketamine-HCl and then decapitated.…”

“…From these lists, top GO terms were selected based off of highest -log10(adjusted-p-value), and top upstream regulators were selected based on the number of predicted targets DEGs. Slice preparation -As described before [14][15][16] . Mice were anesthetized with 150 mg/kg Ketamine-HCl and then decapitated.…”

Functional Magnetic Resonance Imaging and Obesity—Novel Ways to Seen the Unseen

“…Such a view shows the involvement of the reward system in the food intake process. In addition, a chronic HFHS diet has been shown to consistently increase body weight and hyperphagia by inducing a vicious circle and promoting obesity [ 7 ]. Given these facts, it is likely that overconsumption of food eludes the individual’s consciousness.…”