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

突触可塑性是细胞学习和记忆的基础，它是一个动态过程，包括许多离子通道、膜受体和细胞内底物。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传导是很重要的。许多候选分子被认为是调节突触可塑性的关键因素，但其潜在机制尚不完全清楚。确定突触可塑性背后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。这个项目的发现可以广泛地影响我们的社会，通过开发新的治疗方法来治疗神经退行性疾病，如阿尔茨海默病和其他形式的痴呆症，这些疾病对非裔美国人的影响尤为严重。该项目的其他工作包括对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，这些科学家将推动科学创新、创造力和生产力。该项目主要研究rna结合蛋白DJ-1与小电导钙活化钾通道（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Ca2+通道亚单位的表达和活性，这些亚单位可以决定细胞内Ca2+水平。考虑到细胞内Ca2+强烈影响KCa2活性，以及KCa2通道形成突触可塑性的形式，如长期抑郁（LTD），拟议的研究将确定DJ-1/Ca2+通道信号如何调节KCa2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多方面的议程，旨在利用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：(1)发现学习和记忆的关键新机制，(2)产生相关的基于课程的本科生研究经验（CURE）神经元可塑性，以及(3)通过教师参与在当地高中课程中推广神经科学。计划期间将提供机会概念化实践实验和教学讲座材料，作为开发以研究为基础的课程的一部分，旨在提高本科生对神经科学的参与和参与。规划期间还将允许举办讲习班，旨在使当地高中科学教师有能力为他们的学生开发基于神经科学的课程和研究经验。总的来说，这个规划机会将产生一个以团队为导向的研究计划，该计划将扩大对可塑性机制的理解，并为北卡罗来纳州a&t州立大学的本科生和北卡罗来纳州格林斯博罗的当地高中生提供新颖的研究型课程体验。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.