Previous studies had identified the biological players in loss of appetite. One was an immune molecule called interleukin 18 (IL-18), which activates other cells to fight disease. Another was a brain structure called the Bed Nucleus of the Stria Terminalis (BST)--which has a subset of neurons that project to the Lateral Hypothalamus (LH), a brain region that controls appetite.

The challenge was to show how these elements interacted. The new research began with the discovery of the expression of IL-18 receptors in neurons of the anterior BST. With this finding, the researchers had a starting point for tracking the effects of IL-18 in this part of the brain.

Researchers then used an electrophysiological technique called whole-cell patch clamp to record neuronal activity and uncovered a series of events regulating appetite.

In mouse BST brain slices not exposed to IL-18, an excitatory neurotransmitter called glutamate strongly activates a subset of BST neurons projecting to the LH. The activation of these BST-LH neurons leads to the release of an inhibitory neurotransmitter, called gamma-aminobutyric acid (GABA), on target neurons. The GABA release inhibits neuronal activity in the LH.

Put simply, normal amounts of GABA released into LH leads to a normal appetite. IL-18 interferes with this system. When IL-18 binds to its receptors on a specific subset of BST-LH projecting neurons (type III), it reduces glutamate release, leading to less activation of type III neurons, reduced GABA signaling and a loss of appetite.

Studies of mouse behavior supported this finding. Mice with IL-18 injected directly into the anterior BST ate significantly less than mice that received a control substance.

http://www.scripps.edu/news/press/2016/20160504conti.html