NEURAL BASIS OF SPATIAL COGNITION

研究计划描述了一系列的实验，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。在先前的研究中，在海马和丘脑前核中发现了一群神经元，它们的放电与动物的头部方向无关，与动物的行为和空间位置无关。这个空间信号提供了一个模型系统，用于研究初级感觉信息如何通过各种感觉途径进入，转化为代表生物体与其环境的空间关系的“高级认知信号”。在中枢神经系统中完成这种转化的机制尚不清楚。该提案的第一个目的是研究大脑如何处理头部方向（HD）细胞信号。为了解决这个问题，我们采用了四种实验方法：解剖、单单元记录、病变研究和电刺激。在拟议的项目期间，我们将重点了解以下脑区域对HD细胞信号的贡献：丘脑前核、外侧乳头核、脾后皮层和背被盖区。第二项研究将集中在动物在导航和空间任务中如何使用HD细胞。具体来说，我们将确定哪些类型的内部感觉系统（前庭、动觉、光流）参与路径整合，以及每个系统是否足以单独支持路径整合。进一步的实验将确定1)特定的大脑区域是否对路径整合至关重要，2)情景空间信息在没有海马体的情况下可以被编码和检索到的程度，以及3)定向系统的病变如何影响海马体位置细胞放电。最后，我们将探讨HD细胞活动是否以及如何指导动物在工作和参考记忆任务中的行为，以及在需要路径整合才能成功执行的更复杂的导航任务中。拟议实验的结果将深入了解空间信息是如何在大脑中处理的，并对人类健康和行为产生影响。老年患者和阿尔茨海默病患者（一种通常与边缘系统结构的显著病理相关的疾病）通常会经历空间定向障碍，以至于需要持续的监督。了解空间信息是如何在老鼠大脑中处理的，将为我们了解人类空间处理的复杂本质提供线索。

The Research Plan describes a series of experiments which will examine how spatial information is processed 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. During the proposed project period, we will focus on understanding the contributions of the following brain areas to the HD cell signal: anterior thalamic nuclei, lateral mammillary nuclei, retrosplenial cortex, and the dorsal tegmental area. A second line of investigation will focus on how animals use HD cells during navigation and spatial tasks. Specifically, we will determine what types of internal sensory systems (vestibular, kinesthetic, optic flow) are involved in path integration and whether each system alone is sufficient to support path integration. Additional experiments will determine 1) whether particular brain areas are critical for path integration, 2) the extent to which episodic spatial information can be encoded and retrieved without a hippocampus, and 3) how lesions of the directional system affect hippocampal place cell discharge. Finally, we will explore if and how HD cell activity guides an animal's behavior in both working and reference memory tasks and in more complex navigational tasks that require path integration for successful performance. 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 Alzheimers 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.