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Research Project: Developmental Determinants of Obesity in Infants and Children

Location: Children's Nutrition Research Center

Title: GABAergic projections from lateral hypothalamus to paraventricular hypothalamic nucleus promote feeding

item WU, ZHAOFEI - University Of Houston
item KIM, EUR RAN - University Of Houston
item SUN, HAO - University Of Houston
item XU, YUANZHONG - University Of Houston
item MANGIERI, LEANDRA - University Of Houston
item LI, DE-PEI - Md Anderson Cancer Center
item PAN, HUI-LIN - Md Anderson Cancer Center
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item ARENKIEL, BENJAMIN - Baylor College Of Medicine
item TONG, QINGCHUN - University Of Houston

Submitted to: Journal of Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/7/2015
Publication Date: 2/25/2015
Citation: Wu, Z., Kim, E., Sun, H., Xu, Y., Mangieri, L., Li, D., Pan, H., Xu, Y., Arenkiel, B., Tong, Q. 2015. GABAergic projections from lateral hypothalamus to paraventricular hypothalamic nucleus promote feeding. Journal of Neuroscience. 35(8):3312-3318.

Interpretive Summary: Obesity is a serious global health problem. Here we showed that a chemical, namely GABA, can strongly promote food intake through its actions in the brain. These findings suggest that GABA signals in the brain could be a potential target for treatment of obesity.

Technical Abstract: Lesions of the lateral hypothalamus (LH) cause hypophagia. However, activation of glutamatergic neurons in LH inhibits feeding. These results suggest a potential importance for other LH neurons in stimulating feeding. Our current study in mice showed that disruption of GABA release from adult LH GABAergic neurons reduced feeding. LH GABAergic neurons project extensively to the paraventricular hypothalamic nucleus (PVH), and optogenetic stimulation of GABAergic LH->PVH fibers induced monosynaptic IPSCs in PVH neurons, and potently increased feeding, which depended on GABA release. In addition, disruption of GABA-A receptors in the PVH reduced feeding. Thus, we have identified a new feeding pathway in which GABAergic projections from the LH to the PVH promote feeding.