Research Project 5: Estefania Azevedo, PhD

Neurodevelopmental disorders (NDD) affect the development of the nervous system, leading to abnormal brain function which may affect emotion and self-control. Obesity is an important co-morbidity of NDDs and is thought to arise from the impairment of important feeding-relevant circuits. Early life stress (ELS) can remodel feeding relevant circuits and contribute to obesity, yet the underlying mechanisms driving these changes are unknown. The current project aims to provide a link between early life stress and obesity. Our preliminary data show that in adult rodents, chemogenetic inhibition of neurotensin-expressing neurons in the lateral septum (LSNTS) increase standard chow intake. When exposed to HFD, silencing of LSNTS neurons increase HFD intake and accelerate obesity. Interestingly, LSNTS neurons respond to stressful but also to rewarding stimuli (i.e. HFD) and are key to the brain circuitry regulating feeding behavior. Additionally, ELS has been shown to alter neuronal activity in the LS and affect motivated behaviors, such as social interaction. We will extend these preliminary data to test the hypothesis that ELS reprograms LSNTS neurons activity downregulating important molecular pathways, ultimately impacting feeding behavior. The project will benefit from the CNDD cores for behavioral assays, in vivo imaging, bioinformatics approaches, and advanced biostatistical consulting. Specific contribution to CNDD: Dr. Azevedo provides critical expertise to CNDD as an expert in animal behavior, viral tools for circuits neuroscience, feeding and obesity. Her research interests align well with other CNDD members such as Dr. Cowan, Berto and Sato and contributes to the understanding of mechanisms by which environmental factors during development (i.e. stress) affect brain circuits and adult behavior.