Planning: Novel mechanisms of plasticity and cognition: Probing DJ-1 as a key regulator of Calcium/Potassium dynamics

Synaptic plasticity, the cellular basis of learning and memory, is a dynamic process that incorporates a number of ion channels, membrane receptors, and intracellular substrates. Thus, it is important to explore the interplay between these molecules to gain a more complete understanding of coordinated signaling within the central nervous system. A number of candidate molecules have been proposed as key factors in regulating synaptic plasticity, but the underlying mechanisms are incompletely understood. Identifying key mechanisms that underlie synaptic plasticity is pivotal to enhancing our overall understanding of neuronal circuits and their contributions to cognitive processes that influence learning and memory. Discoveries from this project can broadly impact our society through the development of novel therapeutic treatments for neurodegenerative disorders like Alzheimer’s disease and other forms of dementia that disproportionately affect African-Americans. Additional efforts in this project include the education and research training of students who are underrepresented in STEM, thereby, promoting diversity of the next generation of scientists who will drive scientific innovation, creativity, and productivity. The project centers on examining the interactions between the RNA-binding protein DJ-1 and Small-conductance Calcium-activated Potassium channels (KCa2 also known as SK Channels) to regulate plasticity. DJ-1 controls the expression and activity of several Ca2+ channel subunits that can determine intracellular Ca2+ levels. Given that intracellular Ca2+ strongly influences KCa2 activity and that KCa2 channels shape forms of synaptic plasticity such as long-term depression (LTD), proposed studies will determine how DJ-1/Ca2+ channel signaling regulates the expression and function of KCa2 to influence learning and memory. The planning activities for this project encompass a multifaceted agenda aimed to capitalize on shared expertise in neuronal mechanisms of synaptic plasticity and models of cognition to (1) discover key new mechanisms of learning and memory, (2) generate a related course-based undergraduate research experience (CURE) on neuronal plasticity, and (3) promote neuroscience within local high school curriculums through instructor engagement. The planning period will provide opportunities to conceptualize hands-on experiments and didactic lecture materials as part of developing a research-based course aimed at enhancing undergraduate engagement and participation in neuroscience. The planning period will also allow for the hosting of workshops aimed at empowering local high school science instructors to develop neuroscience-based curriculums and research experiences for their students. Collectively, this planning opportunity will generate a team-oriented research proposal that will expand understanding of plasticity mechanisms and produce novel research-based course experiences for undergraduate students at North Carolina A&T State University and for local high school students within Greensboro, NC. 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.