CAREER: Neural circuitry mediating increased feeding during pregnancy

Pregnancy is associated with drastic changes in hormone levels and neural function in mammals, including humans. One important physiological change associated with pregnancy is a significant increase in food intake, which is necessary to provide the essential nutrients required for fetal growth and development. Importantly, overfeeding during pregnancy and/or exposure to processed and nutritionally deficient foods increases the risk of the mother and children developing metabolic disorders later in life, with similar results observed in both humans and in mice. However, little is known about the underlying neurobiological changes mediating increased feeding during pregnancy, and a foundational understanding of these mechanisms is required for optimizing nutrition during pregnancy. Dr. Sweeney’s CAREER award will determine the neural circuitry and molecular mechanism(s) mediating increased feeding during pregnancy in mice, providing foundational insight into the neurobiological effects of pregnancy on neuronal function. In conjunction with the experimental goals of this project, Dr. Sweeney and his team will also establish a course-based undergraduate research experience (CURE) with the goal of retaining students in the biomedical sciences while providing outreach and mentoring to local high school students. Students in this course will directly contribute to the experimental goals of this project, while also developing a teaching module to educate local high school students on topics in neurobiology research. Taken together this proposal will fill a major intellectual gap in the fields of neuroscience and endocrinology while developing new educational and outreach opportunities for the local Champaign-Urbana community. This project advances NSF’s priorities in Biotechnology. The hypothalamic melanocortin system consists of agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. These two populations of neurons exert antagonistic effects on feeding with AgRP neurons promoting feeding and POMC neurons suppressing feeding, and the function of AgRP and POMC neurons is conserved in both mice and humans. Dr. Sweeney and his team propose that arcuate nucleus agouti-related peptide (AgRP) neurons are activated and pro-opiomelanocortin (POMC) neurons are inhibited during pregnancy in mice to promote increased food intake. In this proposal, Dr. Sweeney will first utilize novel longitudinal in vivo calcium imaging to map changes in AgRP and POMC neurons across pregnancy in mice. They will evaluate the effect of pregnancy on the sensitivity of AgRP and POMC neurons to hormonal signals associated with the pregnant state in mammals. The researchers will also utilize brain slice electrophysiological approaches to determine the effect of pregnancy on synaptic plasticity within key hypothalamic populations controlling feeding. Finally, Dr. Sweeney’s team will utilize functional neuroanatomy to establish the effect of sex steroids and hormones on the function of AgRP and POMC neurons during pregnancy. Together, these experiments will elucidate a novel pathway linking pregnancy to altered neuronal function, providing fundamental insights into a critical period of mammalian physiology. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2540763 | Program: 01003031DB NSF RESEARCH & RELATED ACTIVIT,01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Patrick Sweeney | Institution: University of Illinois at Urbana-Champaign, URBANA, IL | Award Amount: $842,968 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2540763 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2540763.html