Genetically Dissecting Basal Forebrain Circuits Underlying Eating Disorders
Abstract
Abnormal eating habits that drive excessive food seeking- or avoidance, can manifest as health-threatening and socially impactful eating disorders. We have previously reported a potent role for basal forebrain cholinergic neurons in regulating feeding behavior, and recently discovered that cell type-specific manipulations of their immediate downstream targets, i.e. Glutamatergic (Glu+) neurons, are capable of directly toggling a spectrum of eating-associated behaviors that range from increased food seeking and excessive food consumption to severe hypophagia, overt food avoidance, and starvation. Continuing on the achievements in the previous report, we have accomplished experiments showing that Glu+ neurons are direct downstream target of cholinergic neurons, the cholinergic receptor types on the Glu+ neurons, Glu+ neuron responses to a variety of external cues including food odors, and potent inhibition on feeding behaviors by activation of Glu+ neurons. In addition, we have also made significant progress in other goals including experiments aimed at testing the effects of loss of function of forebrain Glu+ neurons, the roles of LH neurons in mediating the action of forebrain Glu+ neurons in feeding behaviors, as well as the effect of the forebrain Glu+ neurons on obesity from leptin deficiency, all of which have laid a solid foundation for the planned goals in year 3. Our discoveries to date provide intriguing insight into a previously unknown circuit that links the cholinergic basal forebrain, which is known for its role in attention, wakefulness, and sensory processing, to value based components of eating. Experiments designed in this award will elucidate the mechanisms by which basal forebrain circuits govern food seeking and/or food aversion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1154539
Entities
People
- Bennjamin R. Arenkiel
Organizations
- Baylor College of Medicine