Metaplasticity in the ventral pallidum as a potential marker for the propensity to gain weight in chronic high-calorie diet

Shani Gendelis, Dorrit Inbar, Kineret Inbar, Shanee Mesner, Yonatan M. Kupchik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageAmerican English
Pages (from-to)9725-9735
Number of pages11
JournalJournal of Neuroscience
Issue number50
StatePublished - 9 Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 the authors


  • Motivation
  • Obesity
  • Overeating
  • Patch clamp
  • Synaptic plasticity
  • Ventral pallidum


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