The Role of Early Life Stress in Feeding Behaviors

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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 are 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) increases standard chow intake. When exposed to HFD, silencing of LSNTS neurons increase HFD intake and accelerates 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. In Aim 1, we will employ in vivo calcium imaging to monitor changes in the activity of LSNTS neurons to better understand how ELS alters LSNTS neuronal encoding of rewarding information and how these changes impact binge eating behavior and HFD consumption. In Aim 2, we will use cell type-specific molecular profiling (viralTRAP) and next-generation sequencing to molecularly profile LSNTS neurons in ELS and control mice to assess which specific gene transcripts are altered by ELS. Together, our study will clarify how ELS contributes to obesity by affecting feeding-relevant specific circuits in the brain. The project will benefit from the CNDD cores for behavioral assays, in vivo imaging, bioinformatics approaches, and advanced biostatistical consulting. The career development and mentorship will help the PI obtain future NIH R01 funding to facilitate the transition to an established investigator in the field of neurodevelopment and its disorders.