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

突触可塑性是学习和记忆的细胞基础，是一个由许多离子通道、膜受体和细胞内底物组成的动态过程。因此，探索这些分子之间的相互作用对于更全面地了解中枢神经系统内的协调信号是很重要的。一些候选分子被认为是调节突触可塑性的关键因素，但其潜在的机制尚不完全清楚。识别突触可塑性的关键机制对于增强我们对神经元回路及其对影响学习和记忆的认知过程的贡献的整体理解至关重要。该项目的发现可以通过开发治疗阿尔茨海默病和其他形式的痴呆症等神经退行性疾病的新疗法来广泛影响我们的社会，这些疾病对非裔美国人的影响不成比例。该项目的其他努力包括对STEM中代表性不足的学生进行教育和研究培训，从而促进下一代科学家的多样性，他们将推动科学创新、创造力和生产力。该项目的核心是研究RNA结合蛋白DJ-1和小电导钙激活钾通道(KCa2也称为SK通道)之间的相互作用，以调节可塑性。DJ-1控制几个钙离子通道亚基的表达和活性，这些亚单位可以决定细胞内的钙离子水平。鉴于细胞内Ca~(2+)强烈影响KCa~(2+)活性，以及KCa~(2+)通道形成突触可塑性形式，如长时抑制(LTD)，拟议中的研究将确定DJ-1/Ca~(2+)通道信号如何调节KCa~(2+)的表达和功能，从而影响学习和记忆。该项目的规划活动包括一个多方面的议程，旨在利用在突触可塑性的神经元机制和认知模型方面的共享专业知识来(1)发现关键的新的学习和记忆机制，(2)产生相关的基于课程的本科生关于神经元可塑性的研究经验(CURE)，以及(3)通过教师的参与在当地高中课程中促进神经科学。规划期将提供机会将动手实验和教学教材概念化，作为开发旨在加强本科生对神经科学的参与和参与的研究型课程的一部分。规划期间还将举办讲习班，旨在增强当地高中科学教师的能力，为他们的学生开发以神经科学为基础的课程和研究经验。总而言之，这一规划机会将产生一个以团队为导向的研究提案，它将扩大对塑性机制的理解，并为北卡罗来纳A&P；T州立大学的本科生和北卡罗来纳州格林斯伯勒的当地高中生提供新颖的基于研究的课程体验。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.