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，是一个动态过程，它结合了许多离子通道，膜接收器和细胞内底物。这是重要的是要探索这些分子之间的相互作用，以便对中枢神经系统内的协调信号进行更完整的了解。已经提出了许多候选分子作为确定合成可塑性的关键因素，但是潜在的机制是不完全理解的。确定基于突触可塑性的关键机制对于增强我们对神经元电路的整体理解及其对影响学习和记忆的认知过程的贡献至关重要。该项目的发现可以通过开发新颖的神经退行性疾病治疗治疗，例如阿尔茨海默氏病和其他对非比例影响非裔美国人的痴呆症。该项目中的其他努力包括对STEM中代表性不足的学生的教育和研究培训，从而促进了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。 DJ-1控制了几个CA2+通道亚基的表达和活性，这些CA2+通道亚基可以确定细胞内Ca2+水平。鉴于细胞内Ca2+强烈影响KCA2活性，并且KCA2通道形式形式的突触可塑性，例如长期抑郁症（LTD），建议的研究将决定DJ-1/CA2+通道信号如何调节KCA2的表达和功能以影响学习和记忆。该项目的计划活动涵盖了一个多方面的AGERDA，旨在利用突触可塑性和认知模型的神经元机制的共同专业知识，以（1）发现学习和记忆的关键新机制，（2）在基于课程的本科生研究经验（CUR）（CURE）在范围内通过（CUR）进行了神经元的可塑性，并通过（3）培训Neuross in in Neursistor in in Neuroscience in in Neursistors in in neuroscience in in Neursients in and（3）培训高处。计划期将提供机会，概念化动手实验和教学授课材料，作为开发旨在增强本科参与和参与神经科学的研究课程的一部分。计划期还将允许举办研讨会，旨在授权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。 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 precious of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.