Project Summary One of the key roles of the olfactory system is to guide animals towards things they need and away from things they ought to avoid. Landmark studies have shown that during such spatial navigation in visually defined environments, “grid cells” in rodent entorhinal cortex (ERC), with hexagonally symmetric (6-fold) firing fields, tile the floor of a landscape, providing a metric for self-location and path finding. Such approaches have inspired parallel studies in humans: when subjects explore a 2-D virtual reality arena, identification of 6-fold functional MRI (fMRI) activity in ERC can be used to infer the presence of a grid-like map in the human brain. We have recently shown that human participants can use odor landmarks to navigate a virtual odor environment, with corresponding grid-like activity in ERC and piriform cortex (PCx). To follow up on these findings, we are examining the context-based remapping of grid-like activity in human ERC and PCx with a paradigm that manipulates the reward value of odor landmarks. We are also seeking to expand the scope of the parent grant by testing the more general cognitive-map hypothesis that is thought to underlie spatial and olfactory navigation in hippocampus, ERC, and PCx. Beyond navigation, the cognitive-map hypothesis posits that the hippocampal formation encodes a map of abstract relational knowledge that can be flexibly retrieved to predict sensory information in new environments to aid adaptive behavior. We hypothesize that PCx and the hippocampal formation act as a functional unit to encode a rich map of abstract olfactory relations that, once learned, can be retrieved to facilitate perceptual predictions and decision-making. We will test this hypothesis with an olfactory associative-learning paradigm under 7T fMRI, which will afford us the resolution to probe interactions between PCx and small subregions of the hippocampal formation. Using the well-established principles derived from the cognitive-map hypothesis, this research promises to greatly broaden our understanding of olfactory coding in PCx and the hippocampal formation.