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，是一个动态的过程，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非常重要。许多候选分子已被提出作为调节突触可塑性的关键因素，但其潜在的机制还不完全清楚。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新的治疗方法来广泛影响我们的社会，这些治疗方法用于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，这些疾病对非洲裔美国人的影响不成比例。该项目的其他努力包括对STEM领域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。该项目的中心是研究RNA结合蛋白DJ-1和小电导钙激活钾通道（KCa 2，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Ca 2+通道亚基的表达和活性，这些亚基可以决定细胞内Ca 2+水平。鉴于细胞内Ca 2+强烈影响KCa 2活性，并且KCa 2通道塑造突触可塑性的形式，如长期抑郁（LTD），拟议的研究将确定DJ-1/Ca 2+通道信号传导如何调节KCa 2的表达和功能，以影响学习和记忆。该项目的规划活动包括一个多方面的议程，旨在利用突触可塑性和认知模型的神经元机制的共享专业知识，以（1）发现学习和记忆的关键新机制，（2）生成神经元可塑性的相关课程为基础的本科生研究经验（CURE），以及（3）通过教师参与在当地高中校园内促进神经科学。规划期间将提供机会概念化实践实验和教学讲座材料，作为开发旨在提高本科生参与和参与神经科学的研究课程的一部分。规划期间还将举办研讨会，旨在帮助当地高中科学教师为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建议，这将扩大对可塑性机制的理解，并为北卡罗来纳州&AT州立大学的本科生和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，并已被认为是值得通过使用基金会的智力价值和更广泛的评估支持影响审查标准。

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.