NEURAL MECHANISMS OF DIRECTIONAL ORIENTATION

定向的神经机制

• 批准号: 2674432
• 负责人: JEFFREY Steven TAUBE
• 金额: $ 8.59万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2674432
• 关键词: NMDA receptors; behavior test; behavioral /social science research tag; brain electrical activity; brain mapping; cues; electrostimulus; experimental brain lesion; gamma aminobutyrate; head movements; laboratory rat; neural information processing; orientation; single cell analysis; space perception

The PI has been involved in neuroscience research since 1980 and is currently a full-time faculty member at Dartmouth College. The PI wishes to develop a strong research career in behavioral/system neuroscience and make significant contributions to his field. His areas of interests center on the neurobiological mechanisms underlying higher cognitive processes in mammals, in particular learning/memory and spatial cognition. He currently has 5 full-time students in his laboratory. This award will provide relief from several teaching responsibilities and enable him to focus more time on his research and train students within the laboratory. The Award will also provide time for him to learn several new research techniques related to his studies and develop new venues of research interest. Dartmouth College has committed significant financial resources to Dr. Taube over the next 10 years and wants him to develop a strong neuroscience program at the College. Dartmouth College and its affiliated Medical School have all the resources necessary for Dr. Taube to pursue his research goals. The Research Plan describes a series of experiments which will examine how spatial information is process in the mammalian brain. In previous studies a population of neurons was identified within the hippocampal formation and anterior thalamic nuclei which discharge as a function of the animal's head direction, independent of the animal's behavior and spatial location. This spatial signal provides a model system for examining how primary sensory information, entering through various sensory pathways, is transformed into a "higher level cognitive signal" representing the organism's spatial relationship with its environment. The mechanisms which accomplish this transformation in the central nervous system are not known. The first aim of the proposal is to examine how the head direction (HD) cell signal is processed in the brain. To address this issue, four experimental approaches are pursued: anatomical, single-unit recordings, lesion studies, and electrical stimulation. A second line of investigation will focus on how animals use HD cells in behavior and spatial navigation. To date, head direction cell activity has been recorded only in rats moving freely in a cylindrical environment retrieving food pellets. The proposed studies will evaluate how different behavioral paradigms affect head direction cell activity. Additional experiments will determine l) whether HD cells require volitional motor input for activation, 2) the role of GABAergic interneurons in defining the HD cell's "tuning curve", and 3) the role of NMDA receptors in establishing an animal's spatial orientation in a novel environment. Finally the contributions of vestibular, kinesthetic, optic flow, and motor efferent copy cues on HD cell activity will be assessed. The results from the proposed experiments will provide insight into how spatial information is processed in the brain and have implications for human health and behavior. It is common for elderly patients and patients with Alzheimer's disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will give us clues about the complex nature of spatial processes in humans.

PI自1980年以来一直从事神经科学研究， 目前是达特茅斯学院的全职教师。 PI 的愿望 在行为/系统神经科学领域发展强大的研究事业 为其领域做出重大贡献。他的兴趣领域 以高级认知的神经生物学机制为中心 哺乳动物的过程，特别是学习/记忆和空间 认识。他的实验室目前有5名全日制学生。这 该奖项将减轻多项教学责任， 使他能够将更多的时间集中在他的研究上并培训学生 实验室。该奖项还将为他提供学习一些知识的时间 与他的研究相关的新研究技术并开发新的场所 研究兴趣。达特茅斯学院投入了大量资金 未来 10 年向 Taube 博士提供资源并希望他能够发展 学院有一个强大的神经科学项目。达特茅斯学院及其 附属医学院拥有陶布博士所需的所有资源 去追求他的研究目标。 研究计划描述了一系列实验，将检验 空间信息在哺乳动物大脑中是如何处理的。在之前的 研究在海马体内发现了一群神经元 丘脑前核的形成和放电的函数 动物的头部方向，与动物的行为无关 空间位置。该空间信号提供了一个模型系统 检查初级感官信息如何通过各种途径进入 感觉通路，转化为“更高层次的认知信号” 表示有机体与其环境的空间关系。 中央完成这一转变的机制 神经系统未知。该提案的首要目的是审查 头部方向 (HD) 细胞信号如何在大脑中处理。到 为了解决这个问题，采用了四种实验方法：解剖学、 单个单元记录、病变研究和电刺激。 第二个研究方向将集中于动物如何利用 HD 细胞 行为和空间导航。迄今为止，头部方向细胞活动 仅在圆柱形环境中自由移动的大鼠中记录到 回收食物颗粒。拟议的研究将评估不同的 行为范式影响头部方向细胞的活动。额外的 实验将确定 l) HD 细胞是否需要意志运动 激活输入，2）GABA能中间神经元在定义中的作用 HD 细胞的“调节曲线”，以及 3) NMDA 受体在 在新环境中建立动物的空间定向。 最后，前庭、动觉、视流和 将评估 HD 细胞活性的运动传出复制线索。这 所提出的实验结果将提供关于如何 空间信息在大脑中进行处理并对 人类健康和行为。对于老年患者和患者来说很常见 阿尔茨海默氏病，一种通常与显着相关的疾病 边缘系统结构的病理学，体验空间 迷失方向，需要不断的监督。 了解大鼠大脑如何处理空间信息将给出 我们为人类空间过程的复杂性提供了线索。