Regulation of Feeding Behavior by Optogenetic Activation of Inputs to Lateral Hypothalamus

Abstract

The bed nucleus stria terminalis (BNST) and parabrachial nucleus (PBN) are two brain regions in correspondence with the lateral hypothalamic area (LHA) that are responsible for regulating feeding behavior in mice. It is acknowledged that increasing the activity of GABAergic BNST inputs (which release the inhibitory neurotransmitter GABA) to the LHA inhibits LHA glutamate neurons and increases feeding, whereas increasing activity of glutamatergic PBN inputs (which release the excitatory neurotransmitter glutamate) to the LHA excites local glutamate neurons and decreases feeding. Obesity is a prevalent problem in our society, and therefore it is important to understand the reasons behind excessive food intake habits of humans. To address this issue, we tested for effects of activating the BNST-LHA and PBN-LHA pathways in relation to the satiety state of the mice. We stimulated the BNST and PBN inputs to LHA in fasted and fed mice. We tested the effects of Satiety State (fed vs. fasted) and stimulation Frequency (5-40 Hz) on sucrose seeking behavior of two Groups of mice (ChR2 vs YFP controls). The BNST-LHA pathway tended to show a general increase in feeding behaviors, while the PBN-LHA pathway did not show a significant effect of activation. From these results, further studies can be conducted to explore more about these neural pathways and the mechanisms underlying feeding behaviors. On a broader scale, these findings can inform future therapeutics that could help prevent unhealthy eating habits and obesity.