"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."
The goal of this project is to understand how molecules in the brain help maintain stable function during periods of change such as development and high neuronal activity associated with learning. Alterations in neuronal structure are critical for the function of neuronal networks and are greatly influenced by secreted factors such as neurotrophins. One neurotrophin, brain-derived neurotrophic factor (BDNF), enhances neuronal structure and function particularly in the hippocampus, an area of the brain involved in learning and memory. The aim of the project is to understand how these stimulatory effects of BDNF are counter-balanced to maintain homeostasis. They propose that molecules induced by BDNF such as OrphaninFQ/Nociceptin (OFQ) contribute to balancing the neurotrophin's actions. First, using molecular manipulations to reduce levels of BDNF and OFQ signaling, the PIs will examine whether OFQ and BDNF act in a feedback loop to regulate neuronal structure. These experiments will be performed both in hippocampal neurons in a culture dish and in slices which more closely mimic the brain's architecture. Second, they will explore the signaling cascades downstream of OFQ to understand the mechanism by which OFQ interacts with BDNF and affects neuronal structure. It is expected that cells lacking OFQ signaling will respond more dramatically to BDNF and visa versa suggesting that the two molecules act in a feedback loop to regulate each other's function. The results from these studies will have specific implications for mechanisms underlying homeostasis in the central nervous system so that nothing goes awry during development or learning and broader implications for the understanding of how endogenous secreted molecules regulate cellular function. The proposed studies are designed such that graduate and undergraduate students at UMDNJ-RWJ Medical School will learn state-of-the-art techniques. The principal investigator has a strong history of training female students from minority populations and mentoring young women pursuing careers in science, and represents a role model for these women who are interested in a career in research.