Navigation is a central part of daily life. For some, getting around is easy, while others struggle. Some clinical populations, such as those with Alzheimer’s Disease, display wandering behaviors and extensive disorientation. Working at the interface between immersive virtual reality and neuroimaging techniques, my research uses these complementary approaches to inform questions about how we acquire and use spatial knowledge. In this talk, I will discuss both some of my recent work and current experiments that center on three main themes: 1) how we learn new environments, 2) how the brain tracks spatial information, and 3) how individuals differ in their spatial abilities. My work also examines changes in the brain across the lifespan, including major transitions such as menopause and pregnancy. More broadly, I will discuss how navigation lends insight into processes of human learning and memory. The behavioral and neuroimaging studies presented in this talk inform new frameworks for understanding spatial knowledge, leading to novel approaches to answering the next major questions in navigation, learning, and memory.

Deficits in spatial learning and memory occur in many psychiatric and neurological disorders (e.g., schizophrenia, posttraumatic stress disorder, depression, and Alzheimer’s disease). The neural mechanism of these deficits may involve a distinct loss in specific spatial frames of reference or a loss in coordination across reference frames, such as determining the appropriate action for an allocentric location (e.g., turn right when oriented north at a specific location). Investigation of these basic neurobiological mechanisms underlying spatial navigation is critically important for establishing a complete understanding of the neural underpinnings of spatial deficits in psychiatric disorders and brain diseases. Such investigation will facilitate the development of more precise diagnostic tools and therapeutic interventions to help manage or reverse these diseased and disordered brain states, and on a broader level will further our understanding of the neural basis of episodic memory, recognizing objects from a variety of viewpoints, and even inform understanding of basic organizing principles of the brain.

In this talk, I describe my laboratory’s research program to uncover hippocampal-cortical dynamics that promote the consolidation of memories and support fluid interactions with the environment during navigation. I present results from electrophysiology recordings in rats performing multiple novel tasks designed to engage spatial reference frames, showing that communication between the parietal cortex, hippocampus, and anterior thalamus allows for fluid coordination between body and world centered reference frames. I then describe work demonstrating that pathology in this brain network may underlie impaired navigation in mice and rats modeling tau and Aβ aggregation aspects of AD. Finally, I describe work suggesting that impaired hippocampal-parietal interactions during sleep underlie impaired navigation, including our recent finding that at an early timepoint removing pathology specifically in this circuit using a readily translatable approach recovers brain function and cognition. I conclude with a brief introduction to a new area of research in my laboratory focused on a task for assessing reference frame coordination.