Identification Of Midbrain Neural Circuits Of Feeding Behavior

The term ’feeding’ describes the behavior that happened when the energy intake is less than the energy consumption.This negative energy balance causes appetite,then elicits seeking and consumption of food.As one of the basic behaviors,feeding behavior is essential for energy homeostasis and repoduction of biological populations.Abnormal feeding behavior can disturb energy homeostasis and cause many diseases such as obesity,diabetes and cardiovascular diseases.Extensive studies have showed that the hypothalamus has a central role in energy regulation.The AgRP/POMC neurons in the Arcuate nucleus directly sense the leptin and insulin levels in the blood,then act on the Paraventricular nucleus through the melanocortin pathway that finally induces eating or interrupting eating.Although the hypothalamus has been previously identified as the key brain structure that maintaines energy homeostasis,the downstream pathways and non-canonical neural circuitry involved in feeding behavior remain largely uncharacterized.We sought to examine the possible role of the ventrolateral periaqueductal gray(vlPAG)in feeding regulation of this study.The vlPAG is located in the ventrolateral side of midbrain aqueduct.Recent studies identified that GABAergic neurons in vlPAG are involved in defensive behavior when animals percived threatens.This survival instinct is highly related to feeding behavior as the maximum predation risk for many wild animals is during foraging.In addition,the vlPAG receives direct projections from many brain areas that relate to feeding.These,include the paraventricular hypothalamus(PVH),the LH in the hypothalamus,and the central amygdaloid nucleus(CeA).Therefore,we hypothesize here that the vlPAG may play a role in the regulation of feeding.Here,we combined optogenetics,electrophysiological recording,fiber photometry,immunohistochemistry,mono-synaptic viral tracing,animal behavior assays to investigate the possible role of the vlPAG is involved in feeding regulation and underlying circuits.We found that GABAergic neurons in the vlPAG participate in normal feeding behavior.Suppression of GABAergic neurons in the vlPAG directly,or through the long-projection GABAergic inputs from either the BNST or the LH,is sufficient to induce feeding behavior in well-fed mice.Photostimulation of GABAergic neurons in vlPAG is able to interrupt ongoing feeding in starving mice.Long-term activation of vlPAG GABAergic neurons causes starvation.Particularly,our works for the first time revealed that:1,The GABAergic neurons in vlPAG regulates feeding behavior specifically;2,GABAergic circuitry of BNST-vlPAG/LH-vlPAG plays an important role in regulating feeding behavior.