CAREER: An integrated research-education program to uncover rapid cellular mechanisms by which stress-steroids facilitate context-appropriate behaviors

职业：一项综合研究-教育计划，旨在揭示压力类固醇促进适应环境行为的快速细胞机制

• 批准号: 1351129
• 负责人: Emma Coddington
• 金额: $ 57.5万
• 依托单位: Willamette University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1351129&HistoricalAwards=false
• 关键词: CAREER; integrated; research; education; program

It is often assumed that stress is bad, but is this really true? Addressing this question is critical to understanding how humans and other animals respond to prolong periods of disturbance and retain the capacity to navigate the challenges of life. In this context, stress is not bad, merely an experience to navigate. This project promises to reveal the unknown processes by which animals respond to and cope with acute stress - processes that occur on the rapid timescale from seconds to minutes. The project explores the mechanisms using a combination of neurophysiology, confocal microscopy, and behavior. This approach to understanding how hormones and physiological state affects behavior provides an integrated approach to identify important research questions and design undergraduate courses. Student training is integrated with teaching at all levels and is developed through a combination of research-based courses and collaborative student-faculty research. Undergraduate researchers are involved in all stages of the project from experimental design, data collection, and analysis to dissemination through publications and conference presentations. Through involvement in the project undergraduates will be exposed to state-of-the-art research and receive close faculty mentoring. Students are actively encouraged to pursue careers in science through workshops that develop science self-efficacy, and recruits underrepresented students to research through collaboration with the Pacific Northwest Louis Stokes Alliance for Minority Participation.This research will test the hypothesis that CORT employs disparate cellular mechanisms in a cascade that functions within a rapid time frame of ms to min. This cascade is critical for context-appropriate behavioral responses to occur because neurons respond differently to specific temporal input patterns. We know very little about the cellular mechanisms that enable rapid actions of CORT, or about the ability of CORT to affect context-dependent effects. A long-term goal of the research is to identify and characterize the multiple rapid effects of CORT on those neurons that have clear behavioral relevance. The proposed research will use in vivo single-unit and slice whole cell electrophysiology, behavior, and imaging to investigate the following questions: (1) How do hormones impact neurons on different timescales to affect the selection of context-appropriate behaviors? and (2) How do small ephemeral signaling molecules, endocannabinoids, behave as the switch upon which hormones act? Findings from these studies promise to elucidate two novel mechanisms in which CORT modulates intrinsic electrical properties of behavior-associated neurons and receptor-mediated endocytosis of behavior-regulating hormones. Furthermore, this research offers four significant broader impacts: (1) Advancing discovery and understanding while promoting authentic teaching, training, and learning, because student-training is integrated with teaching at all levels and is developed through a combination of research-based courses and collaborative student-faculty research; (2) Participation of underrepresented groups is actively encouraged through a highly impactful workshop to develop science self-efficacy, and by attracting underrepresented students through collaboration with PNW-LSAMP. (3) Enhancement of infrastructure for research and education through collaboration with an assessment expert to develop tools and methods to evaluate learning outcomes, and development of an imaging workshop for novice faculty and students in the region; (4) Broad dissemination of the findings of this work through public lectures, conference presentations, and peer-reviewed publications.

人们通常认为压力是不好的，但这是真的吗？解决这个问题对于理解人类和其他动物如何应对长时间的干扰并保持应对生活挑战的能力至关重要。在这种情况下，压力并不是坏事，只是一种需要驾驭的经历。这个项目有望揭示动物对急性应激反应和应对的未知过程，这些过程发生在从秒到分钟的快速时间尺度上。该项目利用神经生理学、共聚焦显微镜和行为学的结合来探索这种机制。这种理解激素和生理状态如何影响行为的方法为确定重要的研究问题和设计本科课程提供了一种综合方法。学生培训与各级教学相结合，并通过研究型课程和师生合作研究相结合来发展。本科生研究人员参与项目的所有阶段，从实验设计、数据收集、分析到通过出版物和会议报告传播。通过参与该项目，本科生将接触到最先进的研究成果，并接受教师的密切指导。通过发展科学自我效能的研讨会，积极鼓励学生追求科学事业，并通过与太平洋西北路易斯斯托克斯少数民族参与联盟合作，招募代表性不足的学生进行研究。本研究将验证以下假设：在毫秒到分钟的快速时间框架内，CORT在级联中使用不同的细胞机制。由于神经元对特定的时间输入模式的反应不同，因此该级联对于情境适当的行为反应的发生至关重要。我们对使CORT快速作用的细胞机制知之甚少，也不了解CORT影响环境依赖效应的能力。该研究的长期目标是识别和表征CORT对那些具有明确行为相关性的神经元的多重快速影响。本研究将利用体内单单元和切片全细胞电生理、行为和成像来研究以下问题：(1)激素如何在不同的时间尺度上影响神经元，从而影响情境适当行为的选择？(2)短暂的信号分子内源性大麻素是如何作为激素的开关的？这些研究结果有望阐明两种新的机制，其中CORT调节行为相关神经元的内在电特性和受体介导的行为调节激素的内吞作用。此外，本研究提供了四个重要的更广泛的影响：(1)促进发现和理解，同时促进真实的教学、培训和学习，因为学生培训与各级教学相结合，并通过研究性课程和师生合作研究的结合来发展；(2)通过极具影响力的研讨会积极鼓励代表性不足群体的参与，以发展科学自我效能感，并通过与PNW-LSAMP合作吸引代表性不足的学生。(3)通过与评估专家合作开发评估学习成果的工具和方法，加强研究和教育的基础设施，并为该地区的新手教师和学生开发成像讲习班；(4)通过公开讲座、会议报告和同行评议的出版物广泛传播这项工作的发现。