FELLOW:JENNINGS, J Lateral hypothalamic circuit dynamics underlying binge eating

Project: Research project

Description

Binge eating disorders, characterized by uncontrollable bouts of excessive feeding, are often associated with obesity1. Furthermore, the recent surge in high-fat foods has increased the propensity of binge-eating disorders and obesity-related diseases2. Thus, understanding the effects of high-fat foods on the activity of precise neurophysiological systems that are important for regulating energy balance will be critical to the proper identification of novel therapeutic treatments for binge-eating disorders and obesity. One possible neurocandidate for these disorders is the lateral hypothalamus (LH), a well-conserved brain region that was first defined as the “feeding center” almost half a century ago3. Within the LH, two principal neuronal populations that utilize the neuropeptides, melanin-concentrating hormone (MCH) and neurotensin (NT), are thought to have opposing action on energy balance, as the removal of MCH neurons reduces feeding4 and body weight, while the elimination of NT neurons results in obesity5. However, it remains unclear if these genetically defined neurons alter their activity in response to high-fat food in order to control feeding. Thus, the goals of this proposal are to characterize the neural activity patterns of both cell types during binge-eating episodes in mice, as well as to identify the specific input regions of MCH and NT neurons that become activated from binge eating of high-fat foods. To complete the first goal, I will use in vivo electrophysiology paired with optogenetics to monitor changes in firing patterns in MCH and NT neurons during multiple binge-eating episodes. For the second goal, I will combine recent monosynaptic retrograde rabies virus strategies with Fos-immunohistochemistry to determine if exposure to high-fat foods leads to the activation of specific upstream input regions of MCH and NT neurons, which will help to explain the firing profiles of both cell types during binge eating. Taken together, this proposal will permit novel insight into specific neural signals of binge eating and obesity.
StatusFinished
Effective start/end date5/1/1412/31/14

Funding

  • NIH National Institute of Mental Health (NIMH)

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Bulimia
Neurotensin
Binge-Eating Disorder
Neurons
Fats
Food
Lateral Hypothalamic Area
Obesity
Optogenetics
Rabies virus
Electrophysiology
Neuropeptides
Immunohistochemistry
Body Weight
melanin-concentrating hormone
Brain
Therapeutics
Population