NEURAL MECHANISMS OF DIRECTIONAL ORIENTATION

PI自1980年以来一直参与神经科学研究，并 目前是达特茅斯学院的全职教员。少年派的愿望 在行为/系统神经科学方面发展强大的研究事业和 在他的领域做出了重大贡献。他的兴趣领域 高等认知的神经生物学机制研究中心 哺乳动物的过程，特别是学习/记忆和空间 认知力。他的实验室目前有5名全日制学生。这 获奖将缓解几个教学责任，并 使他有更多的时间专注于他的研究，并在 实验室。该奖项还将为他提供时间学习几个 与他的研究相关的新研究技术和开发新的场所 研究兴趣。达特茅斯学院承诺投入大量资金 在未来10年向陶贝博士提供资源，并希望他发展 学院的一个强大的神经科学项目。达特茅斯学院及其 附属医学院拥有陶贝医生所需的所有资源 去追求他的研究目标。 研究计划描述了一系列实验，这些实验将检验 空间信息是如何在哺乳动物的大脑中处理的。在以前的 研究发现，在海马区有一组神经元 丘脑前核的形成和放电作为 动物的头部方向，与动物的行为和 空间位置。这个空间信号提供了一个模型系统 检查初级感觉信息是如何通过各种不同的 感觉通路，被转化为“更高水平的认知信号” 代表有机体与其环境的空间关系。 在中央实现这一转变的机制 神经系统尚不清楚。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。至 为了解决这个问题，我们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。 第二条线的调查将集中在动物如何使用HD细胞。 行为和空间导航。到目前为止，领导单元格活动 仅在圆柱形环境中自由移动的大鼠身上记录 取回食物颗粒。拟议的研究将评估不同之处 行为范式影响头部方向的细胞活动。其他内容 实验将决定L)HD细胞是否需要意志运动 激活的输入，2)GABA能中间神经元在确定 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向。 最后，前庭、动觉、视流和 将评估HD细胞活动的运动传出复制线索。这个 拟议中的实验结果将为我们提供关于 空间信息在大脑中进行处理，并对 人类的健康和行为。它在老年患者和患者中很常见。 阿尔茨海默氏症，这种疾病通常与明显的 边缘系统结构的病理学，体验空间 迷失了方向，以至于需要不断地监督。 了解空间信息在大鼠大脑中的处理方式将给 我们对人类空间过程的复杂性质提供了线索。

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.