# Behavioral and Neural Substrates of Odor-Guided Navigation in the Human Brain

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $88,452

## Abstract

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.

## Key facts

- **NIH application ID:** 10918465
- **Project number:** 3U01DC019405-03S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jay A Gottfried
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $88,452
- **Award type:** 3
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918465

## Citation

> US National Institutes of Health, RePORTER application 10918465, Behavioral and Neural Substrates of Odor-Guided Navigation in the Human Brain (3U01DC019405-03S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10918465. Licensed CC0.

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