Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.01.073205v1?rss=1 Authors: Lau, B. K., Murphy-Royal, C., Kaur, M., Qiao, M., Gordon, G. R., Bains, J. S., Borgland, S. L. Abstract: Overconsumption of palatable, energy dense food is considered a key driver of the obesity pandemic. The orbitofrontal cortex (OFC) is critical for reward valuation of gustatory signals, yet how the OFC adapts to obesogenic diets is poorly understood. Here we show that an impairment of astrocyte glutamate clearance following extended access to a cafeteria diet reduces GABA release onto layer II/III pyramidal neurons in the lateral OFC in rats. This decrease in GABA tone is due to an increase in extrasynaptic glutamate, which activates metabotropic glutamate receptors (mGluR5) and liberates endocannabinoids. In obese rats, these synaptic impairments were rescued by the nutritional supplement, N-acetylcysteine, which restores glutamate homeostasis. Together, our findings indicate that obesity targets astrocytes to disrupt the delicate balance between excitatory and inhibitory transmission in the lateral OFC. Copy rights belong to original authors. Visit the link for more info