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

规划：可塑性和认知的新机制：探索 DJ-1 作为钙/钾动力学的关键调节剂

• 批准号: 2332058
• 负责人: Farr Niere
• 金额: $ 9.61万
• 依托单位: North Carolina Agricultural & Technical State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2332058&HistoricalAwards=false
• 关键词: Planning; Novel; mechanisms; plasticity; cognition

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.

突触可塑性是学习和记忆的细胞基础，是一个包含许多离子通道、膜受体和细胞内底物的动态过程，因此，探索这些分子之间的相互作用对于更全面地了解协调非常重要。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，识别突触可塑性背后的关键机制对于增强我们对神经元的整体理解至关重要。该项目的发现可以通过开发针对神经退行性疾病（如阿尔茨海默病和其他形式的痴呆症）的新型治疗方法来广泛影响我们的社会，这些疾病对非裔美国人的影响尤为严重。该项目包括对 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，推动科学创新、创造力和生产力。该项目的重点是检查 RNA 结合蛋白之间的相互作用DJ-1 和小电导钙激活钾通道（KCa2 ​​也称为 SK 通道）可调节可塑性，从而控制多个 Ca2+ 通道亚基的表达和活性，从而确定细胞内 Ca2+ 水平。 KCa2 ​​通道形成突触可塑性的形式，例如长期抑郁 (LTD)，拟议的研究将确定 DJ-1/Ca2+ 通道信号传导如何调节突触可塑性的表达和功能KCa2 ​​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神经机制和认知模型的共同专业知识来（1）发现学习和记忆的关键新机制，（2）生成关于神经元可塑性的相关基于课程的本科生研究经验（CURE），以及（3）通过教师参与在当地高中课程中促进神经科学。规划期间将提供概念化实践实验和教学讲座材料的机会，作为开发的一部分。一个旨在提高本科生对神经科学的参与和参与的研究型课程，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。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，并产生新颖的基于研究的课程体验，反映给北卡罗来纳州 A&T 州立大学的本科生和北卡罗来纳州格林斯伯勒市的当地高中生。该奖项是 NSF 的法定使命并已被视为值得通过使用基金会的智力优点和更广泛的影响审查标准进行评估来支持。