A Neural Circuit Link Between Anxiety, Stress and Altered Eating

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Do you stress eat? Based on biology, it’s no wonder our emotions are so tightly linked to feeding. Imagine when we foraged for food away from shelter and into potentially dangerous territories. Feeding has evolved to be tightly linked to our emotions, and the biological systems that control feeding also regulate responses to stressful situations. Brain areas, neurons, neurotransmitters, and peptides which mediate energy homeostasis also have roles in regulating emotions. But what are the precise neural circuit mechanisms? In a new paper in Cell Reports, neuroscientists show how a specific population of neurons in the ventromedial hypothalamus (VMH), a key brain region involved in the control of feeding and stress and anxiety-related behaviors, alters feeding, fat mass, locomotion and anxiety. The authors at MRC London Institute of Medical Sciences and Imperial College London perform a series of elegant behavioral studies combined with optogenetics, chemogenetics, and calcium imaging to study neurons known as steroidogenic factor 1 (SF1), with a confirmed role in the VMH in the regulation of body weight and metabolism. Here they show that activating SF1 neurons decrease feeding and fat mass, but increase anxiety. In contrast, the inhibition of SF1 neurons increases feeding and fat mass and decreases anxiety.

While these results suggest that the suppression of SF1 activity permitted feeding, the authors went on to directly monitor SF1 neuronal activity during feeding-related and stress-induced behavior of freely moving mice to determine an intrinsic role. They used the Inscopix nVista system to record the calcium indicator GCaMP6m expressed specifically in SF1 neurons. They implanted lens probes that reached the ventromedial hypothalamus, deep within the brain and coupled that to Inscopix’s core technology, the head-mounted miniature microscope. They determined the effects of food and stress by placing overnight-fasted animals in a 2-chamber arena with empty pots in the opposite corners. After 10 min of exploration, food and a non-edible object were placed in the different pots for an additional 20 min. They tracked freely moving behavior with neuronal activity using Ethovision XT software. When mice entered the feeding zone, the nVista acquisition software recorded timestamps, and subsequent data were processed using Inscopix data processing software.

Mice deprived of food would normally have a strong motivation to feed, and indeed the authors showed that SF1 activity decreased as mice approached food. However, if the mouse left the food, then an increase in SF1 activity was seen. Moreover, if the mouse experienced a stress from a foot shock, then SF1 activity increased and feeding decreased significantly, consistent with their optogenetic and chemogenetic studies. So, in this case, feeding behavior was associated with low anxiety and high intrinsic SF1 activity.

Human eating behaviors are of course much more complicated, but the parallels are intriguing. Humans display disordered eating behavior associated with stress, anxiety and depression. Some people experience weight loss, but others, experience weight gain, especially with chronic stress. This new study points to possible targets in our understanding of the link between stress and feeding.


Modulation of SF1 Neuron Activity Coordinately Regulates Both Feeding Behavior and Associated Emotional States by Paulius Viskaitis, Elaine E. Irvine, Mark A. Smith, Agharul I. Choudhury, Elisa Alvarez-Curto, Justyna A. Glegola, Darran G. Hardy, Silvia M.A. Pedroni, Maria R. Paiva Pessoa, Anushka B.P. Fernando, Loukia Katsouri, Alessandro Sardini, Mark A. Ungless, Graeme Milligan, Dominic J. Withers. Cell Reports. 2017.

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