A Control Theoretic Approach to Addressing Hippocampal Function

Understanding the interplay between sensory input, endogenous neural dynamics, and behavioral output is key to understanding how the brain works at the level of neural computation. Hippocampal place cells are an ideal system to investigate this closed-loop interaction, as they combine input from self-motion cues and external landmarks to continuously update a dynamic neural network that creates an internal representation of location on a cognitive map. The normal functioning of this system is critical for such cognitive processes as flexible navigation, imagining the future, and autobiographical (episodic) memory. Animals can localize themselves by keeping track of their movements and continuously updating their location on their cognitive map based on these movements—a process called “path integration.” In order for this updating to coincide with the animal's actual displacement in the world, the relationship between physical movement and position updating on the map must be fine-tuned. Previous work in a novel virtual- reality environment demonstrated that external landmarks serve as a teaching signal to guide this fine- tuning process through visual experience—a process called “path integration gain recalibration.” The present Administrative Supplement Request seeks additional funds to purchase the hardware for an upgraded virtual reality apparatus and does not change the Aims of the parent grant, which remain as follows. Aims 1 and 2 investigate neurophysiological mechanisms and behavioral consequences of the plasticity of the path integration computation and in Aims 3 and 4 investigate the signals (such as error signals) that underlie the interactions between landmarks and path integration in the hippocampus that likely drive this plasticity. These experiments will provide fundamental insight into how the brain computes representations of the spatiotemporal context of an organism’s experience, which is thought to constitute the framework that the brain uses to organize, interrelate, and bind the various aspects of an experience and store them as a coherent memory. Such insight will help understand how neurodegenerative disorders, such as Alzheimer’s Disease and other dementias, produce the devastating loss of cognitive function that is the hallmark of these diseases.