The hippocampal formation is critically involved in learning and memory. Neurodegenerative disorders such as Alzheimer's Disease dramatically impact this area, leading to severe and progressive memory loss. The hippocampus appears to be the locus of an allocentric, cognitive map of the external world. This map is critical not only for spatial cognition, but also for the conscious recollection of past experience. The hippocampus is thought to bind the individual items and events of experience within a coherent spatiotemporal framework, allowing the experience to be stored and retrieved as a conscious memory. Decades of investigation of hippocampal place cells and the recent discovery of grid cells have revealed that this cognitive map arises from the interaction of external sensory inputs with endogenously generated neural dynamics (underlying the navigational strategy known as path integration). Classical neurophysiological studies with behaving animals have amply characterized the powerful in?uence of environmental landmarks on the ?ring locations of these spatial cells. Extending this approach to quantitatively investigate the internal processes of path integration has proven technically challenging. Virtual reality technology, in combination with systems theory, offers opportunities to solve these problems. We have designed and constructed a novel apparatus that allows us to manipulate the visual inputs (both landmarks and optic ?ow) available to a rat navigating a real circular track as a function of its movements while preserving normal ambulatory and vestibular experience. Place cells recorded in this apparatus replicate known standard phenomenology. In preliminary experiments, we induced a sustained, increasing con?ict between landmark information and path integration that caused a graceful, coherent dissociation of the place ?elds from the landmarks. We will test the capacity of the system to recalibrate the path integrator when challenged with this sustained con?ict. Further, we will develop a novel approach for isolating the contribution of optic ?ow and other selfmotion cues to the update of the neural representation of position, free of the competing in?uence of landmarks. Speci?cally, we will attempt to decode and control this cognitive representation during behavior through realtime manipulations of the optic ?ow. This approach will form the foundation of a novel research program aimed at a comprehensive analysis of the external vs. internal determinants of the cognitive map. Furthermore, this program may reveal important principles of neural computation relevant to general problems of how the brain integrates external sensory input with internal, cognitive representations, and may generate insights into the disordered thinking and hallucinations that are characteristic of schizophrenia and other mental disorders.
Discoveries from basic systems neuroscience demonstrate that external senses (such as vision) interact with the internally generated, cognitive representations that underlie thoughts, perceptions, experience, expectations, and so on. Cognitive disorganization and memory loss are devastating consequences of numerous forms of neurological and psychiatric disorders, including Alzheimer's Disease, stroke, and schizophrenia. These experiments will provide crucial information about the neural mechanisms that allow information from the external senses to interact adaptively with internally generated, cognitive representations, providing insight into how these processes are disrupted in neurological and psychiatric disease.
