Feeding pathways in the brain can be used to treat obesity. Source: http://www.flickr.com/
The neural circuits in the brain implicated in feeding have been uncovered by a research team from University of North Carolina at Chapel Hill, as published in Science in September 2013 (1).
Previous studies have shown that an area of the brain called the lateral hypothalamus (LH) is involved in motivating behavior, such as feeding. The amygdala, responsible for emotions, can also affect food intake by either activating or inhibiting certain neurons in the LH. If activity in the brain fails to be regulated at certain points along the feeding pathway, that particular brain network will begin to fail, leading to maladaptive feeding behavior.
The research team led by Joshua Jennings sought to understand the feeding circuit between the LH and the extended amygdala using mice as their model animal. They focused on an area of the extended amygdala—the bed nucleus of stria terminalis (BNST)—that regulates feeding and then chose a specific inhibitory pathway that runs from the BNST to the LH. Activating that pathway led to ravenous feeding by the mice.
In humans, high-caloric diets often worsen overeating. The scientists therefore tried to determine if activation or inhibition of the specific BNST pathway they chose could lead mice to prefer one type of food over another. Stimulating the pathway via optogenetics (the use of light in conjunction with light-sensitive ion channels) led mice to choose high-fat and calorie-dense food even if they were well-fed with sufficient energy. Inhibiting the circuit reduced feeding even if the mice were hungry and deprived of food.
After gaining a better understanding of the pathway in the extended amygdala, the scientists studied the LH. The LH is composed of many distinct groups of neurons, so the scientists focused on the neurons targeted by the inhibitory pathway in the BNST.
The targeted neurons in the LH were glutamatergic (and thus inherently excitatory). Activation of the excitatory neurons decreased feeding in hungry mice. Inhibiting the excitatory neurons increased feeding in well-fed mice. This shows that the BNST inhibitory inputs affect feeding by either activating or suppressing LH excitatory neurons.
The particular pathway investigated by researchers brings us one step closer to understanding the idiosyncrasies of human feeding behavior. Future research should focus on mapping the patterns in gene expression and the targets of the LH excitatory neurons, so that better therapies for eating disorders and obesity may then be created.
Reference:
- Jennings, J. H., Rizzi, G., Stamatakis, A. M., Ung, R. L. & Stuber, G. D. (2013). The inhibitory circuit architecture of the lateral hypothalamus orchestrates feeding. Science Mag, 341, 1517-1521. http://dx.doi.org/10.1126/science.1241812.