# Odor Memory Traces in the Mouse Olfactory Cortex

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $413,800

## Abstract

Project Summary/Abstract
Learning and memory are fundamental brain functions, yet their underlying cellular and neural circuit
mechanisms remain poorly understood. Odor memories are exceptionally robust in humans and animals, of
outstanding importance for survival and reproduction, and highly susceptible to neurodegenerative disorders
including Alzheimer Disease. The olfactory (piriform) cortex, where odor perception is thought to first emerge,
has long been suggested to encode odor memories. However, the cellular substrates and circuit mechanisms
of olfactory learning are unknown. Our long-term goal is to understand the cellular and neural circuit
mechanisms of odor perception and memory. The objective of this proposal is to provide a mechanistic
cellular/molecular understanding of how odor memories are encoded and expressed. To achieve this objective
we have developed activity-based intersectional genetic approaches in mice that allow us to identify and
manipulate the activity of piriform neurons that were activated during olfactory learning. Our overall hypothesis
is that odors activate sparse, distributed and functionally diverse piriform neurons, whose activity is necessary
and sufficient for olfactory learning and memory. Aim 1: To determine how manipulating the activity of
odor memory trace cells alters behavior. We will use genetic tagging based on cFos promoter activity (“Fos-
tagging”) to visualize and manipulate the activity of piriform neurons that were activated during olfactory
learning. Our preliminary data provide strong evidence for the necessity of Fos-tagged piriform ensembles for
odor fear memory recall. Aim 2: To determine how learning alters the odor response properties of
piriform ensembles. We will perform chronic two-photon imaging of odor-evoked activity in awake, behaving
mice, before, during, and after aversive and appetitive olfactory conditioning. We will also selectively analyze
the response properties of Fos-tagged piriform neurons that are essential for fear odor memory recall. We will
test the hypothesis that olfactory learning selectively enhances the encoding of stimulus detection and
discriminability in neurons constituting an olfactory memory trace. Aim 3: To determine the molecular
identity and connectivity of olfactory memory trace cells. To drive behaviors, piriform ensembles must
convey odor information to downstream target areas. Using our previously identified set of marker genes and
single cell transcriptomics we will determine the molecular identities of piriform neurons that are activated
during learning, and we will trace their axonal projections. We will test the hypothesis that olfactory learning
facilitates functional connectivity of piriform cortex with task-relevant target areas. This project is innovative
because is combines state-of-the-art genetic, behavioral, imaging and molecular approaches to identify the
cellular and neural circuit substrates for olfactory learning and memory. It is sign...

## Key facts

- **NIH application ID:** 9828598
- **Project number:** 5R01DC017437-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Alexander Fleischmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,800
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828598

## Citation

> US National Institutes of Health, RePORTER application 9828598, Odor Memory Traces in the Mouse Olfactory Cortex (5R01DC017437-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828598. Licensed CC0.

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