NEURAL MECHANISMS OF DIRECTIONAL ORIENTATION

定向的神经机制

• 批准号: 2889842
• 负责人: JEFFREY Steven TAUBE
• 金额: $ 9.02万
• 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 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2889842
• 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年以来一直参与神经科学研究， 目前是达特茅斯学院的全职教师。PI希望 在行为/系统神经科学方面发展强大的研究事业， 为他的领域做出了重大贡献。他的兴趣领域 中心的神经生物学机制的基础上更高的认知 哺乳动物的学习/记忆和空间过程， 认知.目前，他的实验室有5名全日制学生。这 奖励将提供从几个教学责任救济， 使他能够把更多的时间集中在他的研究和培养学生在 实验室该奖项还将提供时间，让他学习几个 新的研究技术与他的研究和开发新的场地， 研究兴趣。达特茅斯学院已经承诺了大量的财政援助 在未来10年内向Taube博士提供资源，并希望他发展 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Taube博士所需的所有资源 来实现他的研究目标 研究计划描述了一系列实验，将检查 哺乳动物大脑是如何处理空间信息的前几 研究发现，在海马神经元中， 形成和前丘脑核，其作为功能放电 动物的头部方向，独立于动物的行为， 空间位置这个空间信号提供了一个模型系统， 研究初级感觉信息如何通过各种 感觉通路，转化为“更高层次的认知信号” 代表有机体与其环境的空间关系。 在中央完成这种转变的机制 神经系统未知。该提案的第一个目的是审查 头部方向（HD）细胞信号在大脑中是如何处理的。到 为了解决这个问题，采用了四种实验方法：解剖学， 单单位记录、损伤研究和电刺激。 第二条研究路线将集中在动物如何使用HD细胞， 行为和空间导航。迄今为止，头部方向细胞活动 只有在圆柱形环境中自由活动的大鼠中才有记录 取回食物颗粒。拟议中的研究将评估 行为范例影响头部方向细胞活性。额外 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“调谐曲线”，以及3）NMDA受体在 在一个新的环境中建立动物的空间定位。 最后，前庭，动觉，视流， 将评估运动传出复制线索对HD细胞活性的影响。的 从拟议的实验结果将提供洞察如何 空间信息是在大脑中处理的， 人类健康和行为。常见于老年患者和 阿尔茨海默病，一种通常与显著的 边缘系统结构的病理学， 在需要持续监督的情况下出现定向障碍。 了解空间信息在老鼠大脑中是如何处理的， 我们对人类空间过程的复杂性的线索。