The impact of early life opioid exposure on the molecular and functional trajectories of septal cell types

Project Summary The use of opioids by pregnant women has increased in recent years, especially the abuse of fentanyl in the US. Opioids increase the risk of pregnancy loss and stillbirth and can cause neonatal opioid withdrawal syndrome (NOWS) in infants, leading to cognitive and behavioral risks in children and adults. However, the neural basis of these deficits is not understood. Animal models suggest that behavioral and cognitive deficits from prenatal opioid exposure are directly caused by persistent opioid exposure, but the cellular and molecular basis of these deficits are largely unknown. The septal complex plays a critical role in addiction, drug-seeking, and stress related behaviors, but it is unclear how specific septal neural cell types contribute to opioid-induced neuroadaptations. It is also unknown if neurodevelopment is a sensitive period where drug-induced changes can become permanent or what cell types and molecular programs are induced by opioid exposure and addictive states in the developing and adult brain. Using scalable complementary cellular and molecular approaches our study will characterize the developmental trajectories and adaptations of neural cell types in the septal complex in a mouse model of early life opioid exposure and withdrawal to address these gaps in knowledge. Our studies will provide a comprehensive catalogue of the cellular, circuit and molecular adaptations that occur in the developing septal complex after fentanyl exposure and determine the key septal cell types that mediate circuit and behavioral adaptations that occur with early life opioid exposure.