CAREER: Noradrenergic Regulation of Hippocampal Interneurons

职业：海马中间神经元的去甲肾上腺素能调节

• 批准号: 0347259
• 负责人: Van Doze
• 金额: $ 58.79万
• 依托单位: University of North Dakota Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0347259&HistoricalAwards=false
• 关键词: CAREER; Noradrenergic; Regulation; Hippocampal; Interneurons

The research supported by this CAREER award examines the role of the naturally occurring neurotransmitter norepinephrine (NE) in the brain and its effects on the physiological functions of interneurons. The excitatory networks of higher brain structures, such as the hippocampus, consist primarily of relay neurons. The activity of these cells is controlled by local inhibitory synaptic interactions, mediated by a small number of specialized cells called interneurons. These interneurons are a diverse group of cells, each presumably responsible for a distinct form of synaptic inhibition. The hippocampus receives a large input of NE-containing fibers, many of which appear to form contacts with interneurons, suggesting that the noradrenergic system may regulate synaptic inhibition through direct actions on interneurons. NE has been implicated in the regulation of sleep, arousal, learning and memory, but our understanding of how different subsets of NE-responsive interneurons modulate these neural processes is incomplete.Evidence suggests that NE differentially regulates at least two discrete, functionally defined, subpopulations of inhibitory hippocampal interneurons. To test this hypothesis, this CAREER project will use an interdisciplinary approach combining electrophysiological, molecular-biological and neuroimaging techniques in the in-vitro rat hippocampus to (i) characterize the effects of NE on different populations of interneurons, (ii) identify the receptors mediating these NE responses, and (iii) determine the morphological profile of interneurons affected by NE. In addition to extending our basic understanding of how NE modulates interneuron function, the information derived from this project may yield important insights into the mechanisms underlying certain cognitive and behavioral states.This investigator will integrate education with his research efforts by developing and teaching in undergraduate- and graduate-level neuroscience courses, and participating in outreach programs to encourage more high-school and undergraduate students (especially women and minorities) to consider and pursue careers in science. As part of the continued mentoring, a team of students will be trained to conduct the proposed research. In addition, benefiting both students and other faculty, the investigator will help establish and direct an electrophysiology core facility. Thus, this CAREER award will not only advance our understanding of how NE affects hippocampal network function, but also allow for high-quality training and research facilities, providing stimulating educational experiences for both present and future generations of neuroscientists.

该职业奖支持的研究探讨了大脑中天然存在的神经递质去甲肾上腺素 (NE) 的作用及其对中间神经元生理功能的影响。 高级大脑结构（例如海马体）的兴奋性网络主要由中继神经元组成。 这些细胞的活动由局部抑制性突触相互作用控制，由少数称为中间神经元的特殊细胞介导。 这些中间神经元是不同的细胞群，每个细胞可能负责不同形式的突触抑制。 海马接收大量含 NE 的纤维输入，其中许多似乎与中间神经元形成接触，表明去甲肾上腺素能系统可能通过对中间神经元的直接作用来调节突触抑制。 NE 与睡眠、觉醒、学习和记忆的调节有关，但我们对 NE 反应性中间神经元的不同子集如何调节这些神经过程的理解并不完整。有证据表明 NE 差异性地调节至少两个离散的、功能上定义的亚群抑制性海马中间神经元。 为了检验这一假设，该 CAREER 项目将在体外大鼠海马中使用一种跨学科方法，结合电生理学、分子生物学和神经影像技术，以 (i) 表征 NE 对不同中间神经元群的影响，(ii) 识别受体介导这些 NE 反应，以及 (iii) 确定受 NE 影响的中间神经元的形态特征。 除了扩展我们对 NE 如何调节中间神经元功能的基本理解外，从该项目中获得的信息可能会对某些认知和行为状态背后的机制产生重要的见解。该研究人员将通过在本科生中进行开发和教学，将教育与其研究工作结合起来。和研究生水平的神经科学课程，并参与外展计划，以鼓励更多的高中生和本科生（特别是女性和少数族裔）考虑和追求科学职业。 作为持续指导的一部分，将培训一组学生来进行拟议的研究。 此外，为了使学生和其他教师受益，研究人员将帮助建立和指导电生理学核心设施。 因此，这个职业奖不仅将增进我们对 NE 如何影响海马网络功能的理解，而且还可以提供高质量的培训和研究设施，为当代和未来几代神经科学家提供刺激的教育体验。