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Understanding the brain circuits involved in eating disorders

Researchers from the University of Washington School of Medicine have found that glutamatergic neurons in mice communicate to two different brain regions: the lateral habenula (a key brain region in the pathophysiology of depression) and the ventral tegmental area (best known for the major role it plays in motivation, reward and addiction). Their recent study, ‘Transcriptional and functional divergence in lateral hypothalamic glutamate neurons projecting to the lateral habenula and ventral tegmental area’, published in Neuron, systematically analysed the lateral hypothalamic glutamate neurons.

Researchers found that, when mice are being fed, the neurons in the lateral habenula are more responsive than those in the ventral tegmental area, suggesting that these neurons may play a greater role in guiding feeding. The study is another step in understanding the brain circuits involved in eating disorders.

"We found these cells are not a monolithic group, and that different flavours of these cells do different things," said Dr Stuber, a joint UW professor of anesthesiology and pain medicine and pharmacology. He works at the UW Center for the Neurobiology of Addiction, Pain, and Emotion, and was the paper's senior author. Mark Rossi, acting instructor of anesthesiology and pain medicine, is the lead author.

The Stuber Lab studies the function of major cell groups in the brain's reward circuit, and characterises their role in addiction and mental illness in hopes of finding treatments. One question is whether these cells can be targeted by drugs without harming other parts of the brain.

Researchers also looked at the influence of the hormones leptin and ghrelin on how we eat. Both leptin and ghrelin are thought to regulate behaviour through their influence on the mesolimbic dopamine system, a key component of the reward pathway in the brain. However, little has been known about how these hormones influence neurons in the lateral hypothalamic area of the brain.

The investigators found that leptin blunts the activity of neurons that project to the lateral habenula and increases the activity of neurons that project to the ventral tegmental area, but ghrelin does the opposite.

This study indicated that brain circuits that control feeding at least partially overlap with brain circuitry involved in drug addiction.


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