Obesity-associated diseases such as diabetes and cardiovascular disease together account for the leading cause of death in the United States. Roughly one-third of the U.S. population is obese, and it is estimated that nearly half of the population will be obese within the next two decades. To date, studies investigating the neural contribution to body weight control have focused largely on neuropeptidergic signaling in the hypothalamus, a key brain region involved in feeding behavior. However, signaling from extra-hypothalamic brain regions has also been implicated in regulating nutrient metabolism, appetite, and satiety. We have recently uncovered a novel mechanism by which glutamatergic signaling in the basal forebrain strongly influences feeding and body weight control. This discovery provides intriguing evidence that specific glutamatergic signaling pathways in the brain critically regulate feeding behavior and body weight homeostasis. To elucidate the mechanisms by which forebrain glutamatergic signaling influences body weight management, feeding behaviors, and metabolism, we will test the hypothesis that glutamatergic basal forebrain circuits modulate metabolic and appetitive programs to regulate body weight. Using a combination conditional genetic targeting, optogenetic manipulations, electrophysiology, and behavioral analysis, we will set out to determine the role for basal forebrain glutamatergic signaling in body weight control and obesity.
We have recently uncovered a novel role for cholinergic basal forebrain glutamatergic neurons in body weight control. This project focuses on elucidating the underlying neurocircuits for the action of glutamatergic neurons in the control feeding and body weight control. Knowledge gained from these studies will provide needed insight into how cholinergic circuits in the central nervous system modulate metabolic and appetitive programs to regulate body weight.
| Liu, Gary; Patel, Jay M; Tepe, Burak et al. (2018) An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice. J Vis Exp : |
| Mangieri, Leandra R; Lu, Yungang; Xu, Yuanzhong et al. (2018) A neural basis for antagonistic control of feeding and compulsive behaviors. Nat Commun 9:52 |
| Hanson, Elizabeth; Swanson, Jessica; Arenkiel, Benjamin R (2017) Sensory experience shapes the integration of adult-born neurons into the olfactory bulb. J Nat Sci 3: |
| John Lin, Chia-Ching; Yu, Kwanha; Hatcher, Asante et al. (2017) Identification of diverse astrocyte populations and their malignant analogs. Nat Neurosci 20:396-405 |
| Yang, Kechun; Broussard, John I; Levine, Amber T et al. (2017) Dopamine receptor activity participates in hippocampal synaptic plasticity associated with novel object recognition. Eur J Neurosci 45:138-146 |
| Liu, Gary; McClard, Cynthia K; Tepe, Burak et al. (2017) Olfactory Cued Learning Paradigm. Bio Protoc 7: |
| Herman, Alexander M; Ortiz-Guzman, Joshua; Kochukov, Mikhail et al. (2016) A cholinergic basal forebrain feeding circuit modulates appetite suppression. Nature 538:253-256 |
