NEURAL BASIS OF SPATIAL COGNITION

该研究计划描述了一系列实验，这些实验将检查哺乳动物大脑中空间信息是如何处理的。在以前的研究中，在海马结构和丘脑前核中发现了一组神经元，这些神经元的放电与动物的头部方向有关，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路径进入的初级感觉信息如何转换为代表有机体与其环境的空间关系的“更高水平的认知信号”。在中枢神经系统中完成这一转变的机制尚不清楚。该提案的第一个目的是研究头部方向(HD)细胞信号在大脑中是如何处理的。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。在拟议的项目期间，我们将重点了解以下脑区对HD细胞信号的贡献：丘脑前核、乳头体外侧核、脾后皮质和背侧被盖区。第二条线的研究将集中在动物在导航和空间任务中如何使用HD细胞。具体地说，我们将确定路径整合涉及哪些类型的内部感觉系统(前庭、运动感觉、视流)，以及每个系统本身是否足以支持路径整合。其他实验将确定1)特定的大脑区域是否对路径整合至关重要，2)情节空间信息在多大程度上可以在没有海马体的情况下进行编码和检索，以及3)定向系统的损伤如何影响海马区细胞放电。最后，我们将探索HD细胞活动是否以及如何在工作记忆和参考记忆任务以及需要路径整合才能成功执行的更复杂的导航任务中指导动物的行为。拟议中的实验结果将为我们深入了解空间信息在大脑中是如何处理的，并对人类的健康和行为产生影响。对于老年患者和阿尔茨海默病患者来说，经历空间定向障碍到需要持续监测的程度是很常见的。阿尔茨海默病是一种经常与边缘系统结构的显著病理相关的疾病。了解空间信息是如何在大鼠大脑中处理的，将给我们提供关于人类空间过程的复杂性质的线索。

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.