Project Summary/Abstract The Research Plan describes a series of experiments that will examine how spatial information is processed in the mammalian brain. In previous studies a population of neurons was identified within the mammillary nuclei anterior thalamus hippocampal formation axis that discharge as a function of the animal's head direction (HD), 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 that accomplish this transformation in the central nervous system are not known. The first aim contains four experiments and is designed to determine how the HD signal is derived and processed from known sensory inputs. Studies will focus on subcortical areas in the brainstem and mammillary nuclei. The second aim will determine the brain areas involved in generating the grid cell signal in medial entorhinal cortex. The third aim addresses the role of two subcortical brain areas that are involved in generating the HD signal in performing a path integration spatial task. In sum, these studies will provide insight into how spatial information is organized and processed in the brain and will enhance our understanding of the functional role of HD cells during navigation. The results will 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.