NEURAL BASIS OF SPATIAL COGNITION

研究计划描述了一系列实验，这些实验将研究哺乳动物大脑如何处理空间信息。 在先前的研究中，在海马结构和丘脑前核内鉴定出一群神经元，其放电作为动物头部方向的函数，与动物的行为和空间位置无关。 这种空间信号提供了一个模型系统，用于检查通过各种感觉通路进入的初级感觉信息如何转化为代表生物体与其环境的空间关系的“更高层次的认知信号”。 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头部方向（HD）细胞信号如何在大脑中处理。 为了解决这个问题，四个实验方法进行：解剖，单单位记录，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的HD细胞信号的贡献：丘脑前核，外侧乳头核，压后皮质，背侧被盖区。第二条研究路线将集中在动物如何在导航和空间任务中使用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支持路径整合。 额外的实验将确定1）特定的大脑区域是否对路径整合至关重要，2）在没有海马的情况下，情节空间信息可以编码和检索的程度，以及3）方向系统的损伤如何影响海马位置细胞放电。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以及更复杂的导航任务中的行为，这些任务需要路径整合才能成功执行。 这些实验的结果将有助于深入了解空间信息在大脑中是如何处理的，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中的显著病理学相关的疾病）通常会经历空间定向障碍，以至于需要持续监督。 了解空间信息在大鼠大脑中的处理方式将为我们提供有关人类空间过程复杂性的线索。

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.