Project Summary/Abstract Reorientation, the navigational process of regaining one’s bearings when lost, is critical for survival and is impaired in several neurodegenerative diseases. Since surface layouts of navigable space tend to be stable over time, lost navigators initially use the geometry of the environment to reorient, despite the presence of directionally informative featural cues, such as visual landmarks, sounds, and/or textures. However, geometric strategies lead to errors in geometrically equivalent locations (e.g., opposite corners of a rectangle). Over repeated exposures to a reorientation context, lost navigators form associations of featural cues and a goal-location, and reorientation becomes guided by features. The hippocampus is well-established for its role in spatial memory, and its cells integrate both geometric and featural cues of the environment. During reorientation, these cells align to the geometry of the environment. However, it is unclear how the hippocampus modulates the relative salience of geometric and featural information during reorientation as animals learn the directional value of featural cues. The retrosplenial cortex (RSC) is a visuospatial processing region that evaluates landmark stability, an inherent property of environmental geometry, and contains cells that are responsive to places, borders, and head- direction on the horizontal plane. Moreover, the RSC is important for environmental learning and lesions to this area impair reorientation. Additionally, the RSC receives monosynaptic, long-range inhibition from GABAergic cells in hippocampal area CA1, a projection that may serve to inhibit the use of geometry during reorientation once associations of featural cues are formed. The goal of this proposal is to investigate how environments are represented in the RSC at the population and single-cell level and the functional role of hippocampal GABAergic projections to RSC during reorientation. To address these questions, this proposal will investigate three aims: 1) Are RSC cell population and single-unit activities correlated with environmental geometry and does RSC activity predict reorientation behavior? This will be assessed using calcium-imaging and single-unit recordings of RSC cells in freely moving mice during reorientation. 2) Does activity of hippocampal GABAergic projections to RSC correlate with behavior in reorientation by features? This will be assessed using pathway-selective calcium- imaging of hippocampal GABAergic cell bodies projecting to RSC during reorientation. 3) Does activation of hippocampal GABAergic projections to RSC impair behavior in reorientation by geometry? This will be assessed using pathway-selective optogenetic activation of hippocampal GABAergic terminals in RSC during reorientation. Under this fellowship, the applicant will continue her training in in vivo electrophysiology and calcium-imaging, honing her skills as an experimentalist. The applicant will also strengthen...